Grupos Investigadores

Líneas de Investigación

  • Análisis de cardiotoxicidad y desarrollo de modelos de cardio-oncología
  • Búsqueda de nuevas estrategias terapéuticas para evitar la degeneración muscular tras lesiones tendinomusculares
  • Estrategias de Ingeniería de Tejidos para el estudio de la Amiloidosis Cardiaca
  • Impresión 3D de miocardio humano terapéutico
  • Reconstrucción de la unidad tendón-músculo mediante ingeniería de tejidos
  • Terapia celular e ingeniería de tejidos en patología osteoarticular

Palabras Clave

  • Degeneración
  • Fabricación aditiva
  • hiPSC
  • Impresión y bioimpresión 3D
  • Músculo esquelético
  • Reparación tisular
  • Tendón

Publicaciones Científicas desde 2018

  • Autores: Llombart Blanco, Rafael; Mariscal, G. (Autor de correspondencia); Barrios, C.; et al.
    Revista: JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
    ISSN: 0002-8614 Vol.72 N° 1 2024 págs. 268 - 279
    Resumen
    Background: Vitamin D deficiency has been linked to numerous health issues, including an increased risk of hip fractures. This meta-analysis aimed to investigate the relationship between vitamin D deficiency and mortality in patients with hip fracture. To assess the impact of different levels of vitamin D deficiency on mortality in patients with hip fractures and examine the influence of potential confounding factors.Methods: A systematic search of PubMed, EMBASE, Scopus, and Cochrane Collaboration Library was conducted, resulting in nine eligible cohort studies (n = 4409). Patients with hip fractures were categorized based on their vitamin D levels as severe, moderate, or insufficient. Mortality was the primary outcome measure in this study. Subgroup analyses were performed according to the follow-up time. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model in Review Manager 5.4.Results: Nine studies, with a pool of 4409 patients, were included. Vitamin D insufficiency was significantly associated with increased mortality (OR 1.24, 95% CI 1.05-1.46; I-2 = 4%). Severe deficiency also led to a significant increase in mortality (OR 2.08, 95% CI 1.09-3.97; I-2 = 42%), whereas moderate deficiency did not show a significant effect (OR 1.06, 95% CI 0.79-1.44; I-2 = 0%). Subgroup analysis revealed significant associations between vitamin D insufficiency and increased mortality at 1-year (OR 1.37, 95% CI 1.06-1.77) and 2-year follow-ups (OR 1.78, 95% CI 1.01-3.15). After adjusting for potential confounders, no significant increase in the mortality rate was observed.Conclusions: This meta-analysis suggests that vitamin D insufficiency and severe deficiency are associated with increased mortality in patients with hip fracture. However, after adjusting for confounding factors, this association was not statistically significant. Further research is necessary to understand the role of vitamin D deficiency in this population.
  • Autores: Paz-Artigas, L.; Montero Calle, Maria del Pilar; Iglesias García, Olalla; et al.
    Revista: INTERNATIONAL JOURNAL OF PHARMACEUTICS
    ISSN: 0378-5173 Vol.632 2023 págs. 122589
    Resumen
    Myocardial ischaemia is one of the leading dead causes worldwide. Although animal experiments have histor-ically provided a wealth of information, animal models are time and money consuming, and they usually miss typical human patient's characteristics associated with ischemia prevalence, including aging and comorbidities. Generating reliable in vitro models that recapitulate the human cardiac microenvironment during an ischaemic event can boost the development of new drugs and therapeutic strategies, as well as our understanding of the underlying cellular and molecular events, helping the optimization of therapeutic approaches prior to animal and clinical testing. Although several culture systems have emerged for the recreation of cardiac physiology, mimicking the features of an ischaemic heart tissue in vitro is challenging and certain aspects of the disease process remain poorly addressed. Here, current in vitro cardiac culture systems used for modelling cardiac ischaemia, from self-aggregated organoids to scaffold-based constructs and heart-on-chip platforms are described. The advantages of these models to recreate ischaemic hallmarks such as oxygen gradients, patho-logical alterations of mechanical strength or fibrotic responses are highlighted. The new models represent a step forward to be considered, but unfortunately, we are far away from recapitulating all complexity of the clinical situations.
  • Autores: Pérez Estenaga, Íñigo; Chevalier, M. T.; Pena, E.; et al.
    Revista: ACS APPLIED MATERIALS AND INTERFACES
    ISSN: 1944-8244 Vol.15 N° 44 2023 págs. 50638 - 50651
    Resumen
    Ischemic heart diseaseis one of the leading causes ofdeath worldwide.The efficient delivery of therapeutic growth factors could counteractthe adverse prognosis of post-myocardial infarction (post-MI). Inthis study, a collagen hydrogel that is able to load and appropriatelydeliver pro-angiogenic stromal cell-derived factor 1 (SDF1) was physicallycoupled with a compact collagen membrane in order to provide the suturestrength required for surgical implantation. This bilayer collagen-on-collagenscaffold (bCS) showed the suitable physicochemical properties thatare needed for efficient implantation, and the scaffold was able todeliver therapeutic growth factors after MI. In vitro collagen matrix biodegradation led to a sustained SDF1 release anda lack of cytotoxicity in the relevant cell cultures. In vivo intervention in a rat subacute MI model resulted in the full integrationof the scaffold into the heart after implantation and biocompatibilitywith the tissue, with a prevalence of anti-inflammatory and pro-angiogenicmacrophages, as well as evidence of revascularization and improvedcardiac function after 60 days. Moreover, the beneficial effect ofthe released SDF1 on heart remodeling was confirmed by a significantreduction in cardiac tissue stiffness. Our findings demonstrate thatthis multimodal scaffold is a desirable matrix that can be used asa drug delivery system and a scaffolding material to promote functionalrecovery after MI.
  • Autores: Ozkan, H.; Di Francesco, M.; Willcockson, H.; et al.
    Revista: DRUG DELIVERY AND TRANSLATIONAL RESEARCH
    ISSN: 2190-393X Vol.13 N° 2 2023 págs. 689 - 701
    Resumen
    Posttraumatic osteoarthritis (PTOA) is mostly treated via corticosteroid administration, and total joint arthroplasty continues to be the sole effective intervention in severe conditions. To assess the therapeutic potential of CCR2 targeting in PTOA, we used biodegradable microplates (mu PLs) to achieve a slow and sustained intraarticular release of the CCR2 inhibitor RS504393 into injured knees and followed joint damage during disease progression. RS504393-loaded mu PLs (RS-mu PLs) were fabricated via a template-replica molding technique. A mixture of poly(lactic-co-glycolic acid) (PLGA) and RS504393 was deposited into 20 x 10 mu m (length x height) wells in a polyvinyl alcohol (PVA) square-patterned template. After physicochemical and toxicological characterizations, the RS504393 release profile from mu PL was assessed in PBS buffer. C57BL/6 J male mice were subjected to destabilization of the medial meniscus (DMM)/sham surgery, and RS-mu PLs (1 mg/kg) were administered intraarticularly 1 week postsurgery. Administrations were repeated at 4 and 7 weeks post-DMM. Drug free-mu PLs (DF-mu PLs) and saline injections were performed as controls. Mice were euthanized at 4 and 10 weeks post-DMM, corresponding to the early and severe PTOA stages, respectively. Knees were evaluated for cartilage structure score (ACS, H&E), matrix loss (safranin O score), osteophyte formation and maturation from cartilage to bone (cartilage quantification), and subchondral plate thickness. The RS-mu PL architecture ensured the sustained release of CCR2 inhibitors over several weeks, with similar to 20% of RS504393 still available at 21 days. This prolonged release improved cartilage structure and reduced bone damage and synovial hyperplasia at both PTOA stages. Extracellular matrix loss was also attenuated, although with less efficacy. The results indicate that local sustained delivery is needed to optimize CCR2-targeted therapies.
  • Autores: Leclerc, K.; Remark, L. H.; Ramsukh, M.; et al.
    Revista: DEVELOPMENT (CAMBRIDGE)
    ISSN: 0950-1991 Vol.150 N° 6 2023 págs. dev201391
    Resumen
    Periosteal stem and progenitor cells (PSPCs) are major contributors to bone maintenance and repair. Deciphering the molecular mechanisms that regulate their function is crucial for the successful generation and application of future therapeutics. Here, we pinpoint Hox transcription factors as necessary and sufficient for periosteal stem cell function. Hox genes are transcriptionally enriched in periosteal stem cells and their overexpression in more committed progenitors drives reprogramming to a naive, self-renewing stem cell-like state. Crucially, individual Hox family members are expressed in a location-specific manner and their stem cell-promoting activity is only observed when the Hox gene is matched to the anatomical origin of the PSPC, demonstrating a role for the embryonic Hox code in adult stem cells. Finally, we demonstrate that Hoxa10 overexpression partially restores the age-related decline in fracture repair. Together, our data highlight the importance of Hox genes as key regulators of PSPC identity in skeletal homeostasis and repair.
  • Autores: Alfonso Olmos-García, Matías (Autor de correspondencia); Llombart Blanco, Rafael; Gil, L.; et al.
    Revista: REVISTA ESPAÑOLA DE CIRUGIA ORTOPEDICA Y TRAUMATOLOGIA
    ISSN: 1888-4415 Vol.67 N° 6 2023 págs. 480 - 486
  • Autores: Pérez Mozas, María (Autor de correspondencia); Payo Ollero, Jesús; Montiel Terrón, Veronica; et al.
    Revista: JOURNAL OF KNEE SURGERY
    ISSN: 1538-8506 Vol.36 N° 1 2023 págs. 79 - 86
    Resumen
    The purpose of this study was to determine if driving ability 6 weeks after anterior cruciate ligament (ACL) reconstruction is affected by the addition of a meniscal suture. It was also hypothesized that no differences in the driving performance would be found between right or left knee surgery subgroups. A total of 82 people participated in this prospective cohort study: 36 healthy controls, 26 patients undergoing isolated ACL (iACL) reconstruction with hamstring autograft, and 20 patients undergoing ACL and meniscal suture (ACL-MS) reconstruction. ACL-MS group followed a weight-bearing and movement restriction protocol during the first 2 postoperative weeks, whereas patients undergoing iACL could start range-of-motion exercises and full weight-bearing ambulation on the first postoperative day. A driving simulator that reproduced real-life driving conditions was used to evaluate driving ability. The software analyzed multiple driving and braking variables. Driving performance in the sixth postoperative week was compared with that of a healthy control group. Subgroup analysis considering additional procedures (iACL, ACL-MS) and the side of the operated knee (right, left) was also performed. No statistically significant differences were found in the demographic characteristics nor in the driving performance (collisions, p =0.897; sidewalk invasions, p =0.749; pedestrian impact, p =0.983) between iACL, ACL-MS, and control groups. No statistically significant differences were found in right-left subgroup analysis. The results of the present study show that patients in their sixth postoperative week after right or left ACL reconstruction showed similar driving performance as compared with a healthy control group, regardless of associating or not a meniscal suture, suggesting it is safe to resume driving 6 weeks after the mentioned surgeries.
  • Autores: Montero Calle, Maria del Pilar; Flandes Iparraguirre, María; Kuebler, B.; et al.
    Revista: STEM CELL RESEARCH
    ISSN: 1873-5061 Vol.71 2023 págs. 103189
    Resumen
    Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a life-threatening disease caused by the abnormal production of misfolded TTR protein by liver cells, which is then released systemically. Its amyloid deposition in the heart is linked to cardiac toxicity and progression toward heart failure. A human induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells (PBMCs) from a patient suffering familial transthyretin amyloid cardio-myopathy carrying a c.128G>A (p.Ser43Asn) mutation in the TTR gene. This iPSC line offers a useful resource to study the disease pathophysiology and a cell-based model for therapeutic discovery.
  • Autores: Moya Jodar, Marta; Ullate Agote, Asier; Barlabe Ginesta, Paula; et al.
    Revista: STEM CELL REPORTS
    ISSN: 2213-6711 Vol.18 N° 1 2023 págs. 64 - 80
    Resumen
    Naive human pluripotent stem cells (hPSCs) are defined as the in vitro counterpart of the human preimplantation embryo's epiblast and are used as a model system to study developmental processes. In this study, we report the discovery and characterization of distinct cell populations coexisting with epiblast-like cells in 5iLAF naive human induced PSC (hiPSC) cultures. It is noteworthy that these populations closely resemble different cell types of the human embryo at early developmental stages. While epiblast-like cells represent the main cell population, interestingly we detect a cell population with gene and transposable element expression profile closely resembling the totipotent eight-cell (8C)-stage human embryo, and three cell populations analogous to trophectoderm cells at different stages of their maturation process: transition, early, and mature stages. Moreover, we reveal the presence of cells resembling primitive endoderm. Thus, 5iLAF naive hiPSC cultures provide an excellent opportunity to model the earliest events of human embryogenesis, from the 8C stage to the peri-implantation period.
  • Autores: Coppiello, Giulia (Autor de correspondencia); Barlabe Ginesta, Paula; Moya Jodar, Marta; et al.
    Revista: DEVELOPMENTAL CELL
    ISSN: 1878-1551 Vol.58 N° 24 2023 págs. 2881 - 2895.e7
    Resumen
    Generating organs from stem cells through blastocyst complementation is a promising approach to meet the clinical need for transplants. In order to generate rejection-free organs, complementation of both parenchymal and vascular cells must be achieved, as endothelial cells play a key role in graft rejection. Here, we used a lineage-specific cell ablation system to produce mouse embryos unable to form both the cardiac and vascular systems. By mouse intraspecies blastocyst complementation, we rescued heart and vascular system development separately and in combination, obtaining complemented hearts with cardiomyocytes and endothelial cells of exogenous origin. Complemented chimeras were viable and reached adult stage, showing normal cardiac function and no signs of histopathological defects in the heart. Furthermore, we implemented the cell ablation system for rat-to-mouse blastocyst complementation, obtaining xenogeneic hearts whose cardiomyocytes were completely of rat origin. These results represent an advance in the experimentation towards the invivo generation of transplantable organs.
  • Autores: Shiroud Heidari, B.; Muiños Lopez, Emma; Harrington, E.; et al.
    Revista: BIOACTIVE MATERIALS
    ISSN: 2452-199X Vol.25 2023 págs. 291 - 306
    Resumen
    Biopolymers play a critical role as scaffolds used in tendon and ligament (TL) regeneration. Although advanced biopolymer materials have been proposed with optimised mechanical properties, biocompatibility, degradation, and processability, it is still challenging to find the right balance between these properties. Here, we aim to develop novel hybrid biocomposites based on poly(p-dioxanone) (PDO), poly(lactide-co-caprolactone) (LCL) and silk to produce high-performance grafts suitable for TL tissue repair. Biocomposites containing 1-15% of silk were studied through a range of characterisation techniques. We then explored biocompatibility through in vitro and in vivo studies using a mouse model. We found that adding up to 5% silk increases the tensile properties, degradation rate and miscibility between PDO and LCL phases without agglomeration of silk inside the com-posites. Furthermore, addition of silk increases surface roughness and hydrophilicity. In vitro experiments show that the silk improved attachment of tendon-derived stem cells and proliferation over 72 h, while in vivo studies indicate that the silk can reduce the expression of pro-inflammatory cytokines after six weeks of implantation. Finally, we selected a promising biocomposite and created a prototype TL graft based on extruded fibres. We found that the tensile properties of both individual fibres and braided grafts could be suitable for anterior cruciate ligament (ACL) repair applications.
  • Autores: Llombart Blanco, Rafael; Mariscal, G. (Autor de correspondencia); Barrios, C.; et al.
    Revista: JOURNAL OF NUTRITION HEALTH AND AGING
    ISSN: 1279-7707 Vol.27 N° 12 2023 págs. 1248 - 1254
    Resumen
    ObjectivesThe objective of this meta-analysis was to investigate the association between hypoalbuminemia and postoperative complications in patients undergoing shoulder arthroplasty.MethodsThis meta-analysis study was registered in PROSPERO (CRD42023442466) and adhered to the PRISMA guidelines. Studies focused on shoulder arthroplasty that compared hypoalbuminemia and normal albumin levels were included. A systematic literature search was conducted in PubMed, EMBASE, Scopus, and the Cochrane Collaboration database. Seven comparative studies were included, and odds ratios with a 95% confidence interval were calculated for the dichotomous variables. A fixed-effect model was used when there was no statistical evidence of heterogeneity, and a random-effect model was used when significant heterogeneity was observed. Review Manager 5.4 software was used for data analysis.ResultsThe meta-analysis included a total of 20,290 patients from seven studies. Hypoalbuminemia was significantly associated with a higher risk of readmissions (OR 2.92, 95%CI 1.74 to 4.91), reoperations (OR 3.23, 95%CI 1.98 to 5.27), an increase in hospital stay duration (MD 1.59, 95%CI 0.86 to 2.32), and complications such as death (OR 5.75, 95% CI 2.98 to 11.08; studies = 4), thromboembolic events (OR 2.43, 95% CI 1.46 to 4.06; studies = 4), cardiac events (OR 2.78, 95% CI 1.07 to 7.24; studies = 3), pulmonary infections (OR 3.09, 95% CI 1.54 to 6.20; studies = 3), systemic infections (OR 2.19, 95% CI 1.51 to 3.16; studies = 3), and transfusions (OR 3.16, 95% CI 2.23 to 4.48; studies = 2). However, there was no significant association between hypoalbuminemia and renal complications, surgical site infections, urinary tract infections, wound problems, or cardiovascular events.ConclusionThis meta-analysis provides strong evidence that hypoalbuminemia is associated with a higher risk of postoperative complications in patients undergoing shoulder arthroplasty.
  • Autores: Lamo de Espinosa Vázquez de Sola, José María; Mariscal, G. (Autor de correspondencia); Gómez Alvarez, Jorge; et al.
    Revista: SCIENTIFIC REPORTS
    ISSN: 2045-2322 Vol.13 N° 1 2023 págs. 17618
    Resumen
    Hip fractures represent a high burden and are associated with mortality in up to 30% of the cases. Stroke complications can be devastating and increase mortality and disability in elderly patients. This study aimed to determine the overall incidence and risk factors for stroke in patients with hip fractures. A systematic search of the literature using PubMed, EMBASE, Scopus, and Cochrane Collaboration Library databases was carried out. Studies have reported the incidence of stroke in patients > 50 years of age with hip fractures. Data were extracted according to PRISMA guidelines (PROSPERO: CRD42023384742). Data were combined using Review Manager version 5.4. A random-effects model was adopted if a significant heterogeneity was observed. The primary outcome was the incidence of stroke in patients with hip fractures. The secondary outcomes of interest included the influence on the incidence of demographic factors, associated conditions, habits, and analytical parameters. Of the 635 initially retrieved studies, 18 were included, with 256,197 patients. The mean age of the patients ranged from 55 to 84 years old. The overall incidence of stroke in patients with hip fracture was 6.72% (95% CI 4.37-9.07%. The incidence of stroke by region was highest in the American continent (8.09%, 95% CI 3.60-12.58%; P>0.001). Regarding associated conditions diabetes significantly increased the risk of stroke (OR 1.80, 95% CI 1.41-2.30). Respect to patient characteristics, BMI greater than 24.4 and female gender did not significantly increase the risk of stroke: (OR 1.07, 95% CI 0.74-1.56) and (OR 1.15, 95% CI 0.91-1.46). Lastly, lower albumin concentrations were a risk factor for stroke in patients with hip fracture (MD - 3.18, 95% CI - 4.06 to 2.31). In conclusion, the incidence of stroke after hip fracture was 6.72%. The incidence of stroke increases over time, and the closely associated risk factors are diabetes and low albumin level.
  • Autores: Spoto, S. (Autor de correspondencia); Argemí Ballbé, José María; Di Costanzo, R. (Autor de correspondencia); et al.
    Revista: JOURNAL OF PERSONALIZED MEDICINE
    ISSN: 2075-4426 Vol.13 N° 7 2023 págs. 1155
    Resumen
    Background: Acute heart failure (AHF) is a major cause of hospitalization and mortality worldwide. Early and accurate diagnosis, as well as effective risk stratification, are essential for optimizing clinical management and improving patient outcomes. In this context, biomarkers have gained increasing interest in recent years as they can provide important diagnostic and prognostic information in patients with AHF. Aim and Methods: The primary objective of the present study was to compare the levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-adrenomedullin (MR-proADM), and C-reactive protein (CRP) between patients diagnosed with acute heart failure (AHF) and those without AHF and sepsis. Furthermore, the study aimed to assess the diagnostic and prognostic value of the use of a multimarker approach in AHF patients. To achieve these objectives, a total of 145 patients with AHF and 127 patients without AHF and sepsis, serving as the control group, were consecutively enrolled in the study. Results: Levels of MR-proADM (median: 2.07; (25th-75th percentiles: 1.40-3.02) vs. 1.11 (0.83-1.71) nmol/L, p < 0.0001), and NT-proBNP (5319 (1691-11,874) vs. 271 (89-931.5) pg/mL, p < 0.0001) were significantly higher in patients with AHF compared to controls, whereas CRP levels did not show significant differences. The mortality rate in the AHF group during in-hospital stay was 12%, and the rate of new re-admission for AHF within 30 days after discharge was 10%. During in-hospital follow-up, Cox regression analyses showed that levels of NT-proBNP > 10,132 pg/mL (hazard ratio (HR) 2.97; 95% confidence interval (CI): 1.13-7.82; p = 0.0284) and levels of MR-proADM > 2.8 nmol/L (HR: 8.57; CI: 2.42-30.28; p = 0.0009) predicted mortality. The combined use of MR-proADM and NT-proBNP provided significant additive predictive value for mortality and new re-admission for AHF at 30 days after discharge. A logistic regression analysis showed that the presence of NT-proBNP pg/mL > 12,973 pg mL and/or MR-proADM > 4.2 nmol/L predicted hospital re-admission within 30 days (OR: 3.23; CI: 1.05-9.91; p = 0.041). Conclusion: The combined assay of MR-proADM and NT-proBNP could be helpful in accurately identifying AHF and in defining prognosis and re-admission for AHF. The complementary use of these biomarkers can provide a useful clinical evaluation of AHF while also orienting clinicians to the pathophysiology underlying heart damage and assisting them in tailoring therapy.
  • Autores: Silva González, Álvaro Antonio; Llombart Blanco, Rafael (Autor de correspondencia); Gallegos-Angulo, M.; et al.
    Revista: GLOBAL SPINE JOURNAL
    ISSN: 2192-5682 Vol.13 N° 1 2023 págs. 156 - 163
    Resumen
    Study Design: Animal experimental model. Objective: To study the clinical behavior and histological changes in the spinal cord, nerve roots and perivertebral muscles of the spine after induced leakage of polymethylmethacrylate (PMMA) loaded with antiblastic drugs during vertebroplasty in an animal model of pigs. Methods: We performed vertebroplasty on 25 pigs. The animals were divided into 3 groups: vertebroplasty with PMMA alone (control group), vertebroplasty with PMMA loaded with methotrexate (MTX) and vertebroplasty with PMMA loaded with cisplatin (CYS). At 2 vertebral levels, epidural and prevertebral, massive cement leaks were induced. Animals were evaluated daily. Two weeks later, the pigs were sacrificed, and the tissues that came in contact with the cement were analyzed. Results: The clinical results for each of the groups were reported. The control group had no clinical alterations. In the MTX group, 2 pigs died before 1 week due to pneumonitis. In the CYS group, 4 animals had motor impairment, and 3 of the 4 had paraplegia. The histological results were as follows: the control and MTX groups showed synovial metaplasia, inflammatory reaction, crystal deposits, and giant cell reaction in the dura mater and muscle and all the animals in the CYS group had spinal cord and muscular necrosis. Conclusions: Massive cement leak after vertebroplasty with PMMA loaded with cisplatin is extremely toxic to the spinal cord and muscles around the spine. Therefore, its use cannot be recommended for the treatment of vertebral metastases. Using PMMA loaded with methotrexate seems to be a safe procedure, but further research is needed.
  • Autores: Romero Torrecilla, Juan Antonio; Lamo de Espinosa Vázquez de Sola, José María; Ripalda Cemborain, Purificación; et al.
    Revista: NPJ REGENERATIVE MEDICINE
    ISSN: 2057-3995 Vol.8 N° 1 2023 págs. 54
    Resumen
    During bone regeneration, the periosteum acts as a carrier for key regenerative cues, delivering osteochondroprogenitor cells and crucial growth factors to the injured bone. We developed a biocompatible, 3D polycaprolactone (PCL) melt electro-written membrane to act as a mimetic periosteum. Poly (ethyl acrylate) coating of the PCL membrane allowed functionalization, mediated by fibronectin and low dose recombinant human BMP-2 (rhBMP-2) (10-25 mu g/ml), resulting in efficient, sustained osteoinduction in vitro. In vivo, rhBMP-2 functionalized mimetic periosteum demonstrated regenerative potential in the treatment of rat critical-size femoral defects with highly efficient healing and functional recovery (80%-93%). Mimetic periosteum has also proven to be efficient for cell delivery, as observed through the migration of transplanted periosteum-derived mesenchymal cells to the bone defect and their survival. Ultimately, mimetic periosteum demonstrated its ability to deliver key stem cells and morphogens to an injured site, exposing a therapeutic and translational potential in vivo when combined with unprecedentedly low rhBMP-2 doses.
  • Autores: Heidari, B. S. (Autor de correspondencia); Muiños Lopez, Emma; Chen, P.; et al.
    Revista: MATERIALS TODAY BIO
    ISSN: 2590-0064 Vol.22 2023 págs. 100778
    Resumen
    The interface tissue between bone and soft tissues, such as tendon and ligament (TL), is highly prone to injury. Although different biomaterials have been developed for TL regeneration, few address the challenges of the TL bone interface. Here, we aim to develop novel hybrid nanocomposites based on poly(p-dioxanone) (PDO), poly (lactide-co-caprolactone) (LCL), and hydroxyapatite (HA) nanoparticles suitable for TL-bone interface repair. Nanocomposites, containing 3-10% of both unmodified and chemically modified hydroxyapatite (mHA) with a silane coupling agent. We then explored biocompatibility through in vitro and in vivo studies using a subcutaneous mouse model. Through different characterisation tests, we found that mHA increases tensile properties, creates rougher surfaces, and reduces crystallinity and hydrophilicity. Morphological observations indicate that mHA nanoparticles are attracted by PDO rather than LCL phase, resulting in a higher degradation rate for mHA group. We found that adding the 5% of nanoparticles gives a balance between the properties. In vitro experiments show that osteoblasts' activities are more affected by increasing the nanoparticle content compared with fibroblasts. Animal studies indicate that both HA and mHA nanoparticles (10%) can reduce the expression of pro inflammatory cytokines after six weeks of implantation. In summary, this work highlights the potential of PDO/ LCL/HA nanocomposites as an excellent biomaterial for TL-bone interface tissue engineering applications.
  • Autores: Siguero-Álvarez, M.; Salguero-Jiménez, A.; Grego-Bessa, J.; et al.
    Revista: CIRCULATION
    ISSN: 0009-7322 Vol.147 N° 1 2023 págs. 47 - 65
    Resumen
    Background: The complex genetics underlying human cardiac disease is evidenced by its heterogenous manifestation, multigenic basis, and sporadic occurrence. These features have hampered disease modeling and mechanistic understanding. Here, we show that 2 structural cardiac diseases, left ventricular noncompaction (LVNC) and bicuspid aortic valve, can be caused by a set of inherited heterozygous gene mutations affecting the NOTCH ligand regulator MIB1 (MINDBOMB1) and cosegregating genes. Methods: We used CRISPR-Cas9 gene editing to generate mice harboring a nonsense or a missense MIB1 mutation that are both found in LVNC families. We also generated mice separately carrying these MIB1 mutations plus 5 additional cosegregating variants in the ASXL3, APCDD1, TMX3, CEP192, and BCL7A genes identified in these LVNC families by whole exome sequencing. Histological, developmental, and functional analyses of these mouse models were carried out by echocardiography and cardiac magnetic resonance imaging, together with gene expression profiling by RNA sequencing of both selected engineered mouse models and human induced pluripotent stem cell-derived cardiomyocytes. Potential biochemical interactions were assayed in vitro by coimmunoprecipitation and Western blot. Results: Mice homozygous for the MIB1 nonsense mutation did not survive, and the mutation caused LVNC only in heteroallelic combination with a conditional allele inactivated in the myocardium. The heterozygous MIB1 missense allele leads to bicuspid aortic valve in a NOTCH-sensitized genetic background. These data suggest that development of LVNC is influenced by genetic modifiers present in affected families, whereas valve defects are highly sensitive to NOTCH haploinsufficiency. Whole exome sequencing of LVNC families revealed single-nucleotide gene variants of ASXL3, APCDD1, TMX3, CEP192, and BCL7A cosegregating with the MIB1 mutations and LVNC. In experiments with mice harboring the orthologous variants on the corresponding Mib1 backgrounds, triple heterozygous Mib1 Apcdd1 Asxl3 mice showed LVNC, whereas quadruple heterozygous Mib1 Cep192 Tmx3;Bcl7a mice developed bicuspid aortic valve and other valve-associated defects. Biochemical analysis suggested interactions between CEP192, BCL7A, and NOTCH. Gene expression profiling of mutant mouse hearts and human induced pluripotent stem cell-derived cardiomyocytes revealed increased cardiomyocyte proliferation and defective morphological and metabolic maturation. Conclusions: These findings reveal a shared genetic substrate underlying LVNC and bicuspid aortic valve in which MIB1-NOTCH variants plays a crucial role in heterozygous combination with cosegregating genetic modifiers.
  • Autores: Iglesias García, Olalla; Ullate Agote, Asier; Montero Calle, Maria del Pilar; et al.
    Revista: TISSUE ENGINEERING PART A
    ISSN: 1937-3341 Vol.29 N° 13 - 14 2023
  • Autores: Flandes Iparraguirre, María; Montero Calle, Maria del Pilar; Iglesias García, Olalla; et al.
    Revista: TISSUE ENGINEERING PART A
    ISSN: 1937-3341 Vol.29 N° 11-12 2023 págs. 237 - 238
  • Autores: Pérez Araluce, María; Cianciosi, A.; Sanmartín Grijalba, Carmen; et al.
    Revista: TISSUE ENGINEERING PART A
    ISSN: 1937-3341 Vol.29 N° 13 - 14 2023
  • Autores: Montero Calle, Maria del Pilar; Calatayud-Sanchez, A.; Gavira Gómez, Juan José; et al.
    Revista: TISSUE ENGINEERING PART A
    ISSN: 1937-3341 Vol.29 N° 11-12 2023 págs. 1377 - 1378
  • Autores: Sánchez Bueno, Andrea; Montero Calle, Maria del Pilar; Larequi Ardanáz, Eduardo; et al.
    Revista: TISSUE ENGINEERING PART A
    ISSN: 1937-3341 Vol.29 N° 13 - 14 2023
  • Autores: Muiños Lopez, Emma; Guaresti, O.; Urtaza, U.; et al.
    Revista: TISSUE ENGINEERING PART A
    ISSN: 1937-3341 Vol.29 N° 13 - 14 2023
  • Autores: Fernández-Santos, M. E. (Autor de correspondencia); García-Arranz, M.; Andreu Oltra, Enrique José; et al.
    Revista: FRONTIERS IN IMMUNOLOGY
    ISSN: 1664-3224 Vol.13 2022 págs. 918565
    Resumen
    MSCs products as well as their derived extracellular vesicles, are currently being explored as advanced biologics in cell-based therapies with high expectations for their clinical use in the next few years. In recent years, various strategies designed for improving the therapeutic potential of mesenchymal stromal cells (MSCs), including pre-conditioning for enhanced cytokine production, improved cell homing and strengthening of immunomodulatory properties, have been developed but the manufacture and handling of these cells for their use as advanced therapy medicinal products (ATMPs) remains insufficiently studied, and available data are mainly related to non-industrial processes. In the present article, we will review this topic, analyzing current information on the specific regulations, the selection of living donors as well as MSCs from different sources (bone marrow, adipose tissue, umbilical cord, etc.), in-process quality controls for ensuring cell efficiency and safety during all stages of the manual and automatic (bioreactors) manufacturing process, including cryopreservation, the use of cell banks, handling medicines, transport systems of ATMPs, among other related aspects, according to European and US legislation. Our aim is to provide a guide for a better, homogeneous manufacturing of therapeutic cellular products with special reference to MSCs.
  • Autores: Egea-Zorrilla, A.; Vera Álvarez, Laura; Sáez Ochoa, Borja; et al.
    Revista: CELLS
    ISSN: 2073-4409 Vol.11 N° 16 2022 págs. 2595
    Resumen
    The lung epithelium is constantly exposed to harmful agents present in the air that we breathe making it highly susceptible to damage. However, in instances of injury to the lung, it exhibits a remarkable capacity to regenerate injured tissue thanks to the presence of distinct stem and progenitor cell populations along the airway and alveolar epithelium. Mechanisms of repair are affected in chronic lung diseases such as idiopathic pulmonary fibrosis (IPF), a progressive life-threatening disorder characterized by the loss of alveolar structures, wherein excessive deposition of extracellular matrix components cause the distortion of tissue architecture that limits lung function and impairs tissue repair. Here, we review the most recent findings of a study of epithelial cells with progenitor behavior that contribute to tissue repair as well as the mechanisms involved in mouse and human lung regeneration. In addition, we describe therapeutic strategies to promote or induce lung regeneration and the cell-based strategies tested in clinical trials for the treatment of IPF. Finally, we discuss the challenges, concerns and limitations of applying these therapies of cell transplantation in IPF patients. Further research is still required to develop successful strategies focused on cell-based therapies to promote lung regeneration to restore lung architecture and function.
  • Autores: Antoñanzas Pérez, Javier; Pelacho Samper, Beatriz; Alkorta Aranburu, Gorka; et al.
    Revista: EXPERIMENTAL DERMATOLOGY
    ISSN: 0906-6705 Vol.31 N° 10 2022 págs. 1638 - 1640
  • Autores: Montiel Terrón, Veronica (Autor de correspondencia); Valentí Azcárate, Andrés; Villas Tomé, Carlos; et al.
    Revista: ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY
    ISSN: 0936-8051 Vol.142 N° 8 2022 págs. 1793 - 1800
    Resumen
    Purpose A question still remains as to whether constrictive toe-box shoes (TBS) cause disability only due to pain on pressure points or if they can cause permanent changes in the hallux anatomy. The aim of this study is to compare the hallux morphology in 3 groups classified according to their use of constrictive or open TBS. Methods 424 patients were classified into 3 groups: group A used open TBS daily; group B used constrictive TBS daily; group C used both open and constrictive TBS. Hallux's angles, presence of exostoses and shape of the distal phalanx (DP) were analyzed on dorsoplantar weight-bearing radiographs and compared amongst groups. Results The intermetatarsal (IMA), metatarsophalangeal (MTPA), DASA, PASA, interphalangeal (IPA), obliquity (AP1), asymmetry (AP2) and joint deviation (JDA) angles for group A were 10 degrees, 8 degrees, 5 degrees, 4 degrees, 9 degrees, 3 degrees, 5 degrees, 3 degrees; for group B were 9 degrees, 19 degrees, 5 degrees, 6 degrees, 12 degrees, 2 degrees, 8 degrees, 2 degrees; and for group C were 10 degrees, 10 degrees, 4 degrees, 4 degrees, 12 degrees, 3 degrees, 8 degrees, 1 degrees. Only the differences in the MTPA, IPA and AP2 were statistically significant (p < 0.05). The prevalence of exostoses on the tibial side of the DP was 22, 36, and 29% in groups A, B and C, respectively (p < 0.05). We found similar distributions of the different DP shapes in the three groups. Conclusions Our results suggest that the use of constrictive TBS, even if used only occasionally, could change hallux anatomy from a young age increasing MTPA, IPA and AP2. Moreover, we have found that DP exostoses are present as a "normal variation" in patients who wear an open TBS, but their prevalence is higher in those wearing constrictive toe-box shoes. This could be due to a reactive bone formation secondary to the friction caused by the inner border of the shoe. Level of clinical evidence 3.
  • Autores: Aguado Álvaro, Laura Pilar; Garitano-Larrea, N.; Abizanda Sarasa, Gloria María; et al.
    Revista: BIOMEDICINES
    ISSN: 2227-9059 Vol.10 N° 10 2022 págs. 2350
    Resumen
    Several Cre recombinase transgenic mouse models have been generated for cardiac fibroblast (CF) tracking and heart regulation. However, there is still no consensus on the ideal mouse model to optimally identify and/or regulate these cells. Here, a comparative evaluation of the efficiency and specificity of the indirect reporter Cre-loxP system was carried out in three of the most commonly used fibroblast reporter transgenic mice (Pdgfra-CreERT2, Col1a1-CreERT2 and PostnMCM) under healthy and ischemic conditions, to determine their suitability in in vivo studies of cardiac fibrosis. We demonstrate optimal Cre recombinase activity in CF (but also, although moderate, in endothelial cells (ECs)) derived from healthy and infarcted hearts in the PDGFRa-creERT2 mouse strain. In contrast, no positive reporter signal was found in CF derived from the Col1a1-CreERT2 mice. Finally, in the PostnMCM line, fluorescent reporter expression was specifically detected in activated CF but not in EC, which leads us to conclude that it may be the most reliable model for future studies on cardiovascular disease. Importantly, no lethality or cardiac fibrosis were induced after tamoxifen administration at the established doses, either in healthy or infarcted mice of the three fibroblast reporter lineages. This study lays the groundwork for future efficient in vivo CF tracking and functional analyses.
  • Autores: Perelli, S. (Autor de correspondencia); Costa, G. G.; Montiel Terrón, Veronica; et al.
    Revista: AMERICAN JOURNAL OF SPORTS MEDICINE
    ISSN: 0363-5465 Vol.50 N° 14 2022 págs. 3778 - 3785
    Resumen
    Background: The increase in anterior cruciate ligament (ACL) injuries in pediatric patients and the high failure rate reported in the literature in this population are driving surgeons to search for specific techniques to better restore knee stability. Recent literature has reported that the combination of lateral extra-articular tenodesis (LET) and ACL reconstruction improves outcomes in high-risk patients. However, such advantages in pediatric patients have been infrequently evaluated. Purpose: To assess whether adding LET to ACL reconstruction can significantly improve knee stability, clinical outcomes, and failure rates in pediatric patients. Study Design: Cohort study; Level of evidence, 3. Methods: A multicentric study involving 3 orthopaedic teaching centers was conducted to evaluate pediatric patients aged between 12 and 16 years who had undergone primary ACL reconstruction using a physeal-sparing femoral tunnel drilling technique. A minimum 2-year follow-up evaluation was required. Based on the surgical technique performed, the patients were divided into 2 group. The patients in group 1 underwent an isolated arthroscopic ACL reconstruction, while the patients in group 2 had an arthroscopic ACL reconstruction in combination with a modified Lemaire LET procedure. Group 1 was a historical control cohort of patients, whereas group 2 was prospectively enrolled. All the patients included in the present study were clinically evaluated using the Pediatric International Knee Documentation Committee (Pedi-IKDC) subjective score and the Pediatric Functional Activity Brief Scale (Pedi-FABS) score. Anteroposterior knee stability was measured using the KT-1000 knee ligament arthrometer, and the objective pivot-shift evaluation was documented using a triaxial accelerometer (Kinematic Rapid Assessment [KiRA]). The included patients also underwent a standardized radiological protocol to evaluate leg-length discrepancies, axial deviation, and degenerative signs preoperatively and at last follow-up. Results: This study included 66 pediatric patients with an anatomic hybrid ACL reconstruction using an autologous 4-strand hamstring graft. In group 1, there were 34 patients (mean age, 13.5 +/- 1.2 years), while 32 patients (mean age, 13.8 +/- 1.4 years) were included in group 2. The clinical outcome scores showed no difference between the 2 groups (Pedi-IKDC, P = .072; Pedi-FABS, P = .180). Nevertheless, the patients in group 2 had better anteroposterior stability measured using a KT-1000 arthrometer (1.9 +/- 1.1 mm in group 1 vs 0.8 +/- 0.8 mm in group 2; P = .031), as well as better rotational stability measured using the KiRA (-0.59 +/- 1.05 m/s(2) in group 2 vs 0.98 +/- 1.12 m/s(2) in group 1; P = .012). The patients in group 1 returned to sports at the same competitive level at a rate of 82.4%, while patients included in group 2 returned at the same competitive level in 90.6% of the cases without a significant difference between the 2 groups (P = .059). No leg-length discrepancies were found between the 2 groups at last follow-up (P = .881). Two patients displayed an increased valgus deformity of 3 degrees on the operated limb at last follow-up (1 patient in group 1 and 1 patient in group 2). Group 1 had a significatively higher cumulative failure rate (14.7% vs 6.3%; P = .021). No intra- or postoperative complications was observed between the 2 groups. Conclusion: Performing a modified Lemaire LET along with an ACL reconstruction with hamstring graft in pediatric patients reduced the cumulative failure rate and improved objective stability with no increase in intra- or postoperative complications. No significant difference was found between the 2 groups in terms of patient-reported outcomes or in the return-to-sports activity.
  • Autores: Ontoria-Oviedo, I.; Amaro-Prellezo, E.; Castellano, D.; et al.
    Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
    ISSN: 1422-0067 Vol.23 N° 17 2022 págs. 9918
    Resumen
    Impaired wound healing in patients with type 2 diabetes (DM2) is characterized by chronic inflammation, which delays wound closure. Specialized pro-resolving lipid mediators (SPMs) are bioactive molecules produced from essential polyunsaturated fatty acids (PUFAs), principally omega-3 docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). SPMs are potent regulators of inflammation and have been used to suppress chronic inflammation in peripheral artery disease, non-alcoholic fatty liver disease, and central nervous system syndromes. LIPINOVA® is a commercially available safe-grade nutritional supplement made from a fractionated marine lipid concentrate derived from anchovy and sardine oil that is rich in SPMs and EPA, as well as DHA precursors. Here, we assessed the effect of LIPINOVA® in wound dressing applications. LIPINOVA® showed biocompatibility with keratinocytes and fibroblasts, reduced the abundance of pro-inflammatory macrophages (M¿1), and promoted in vitro wound closure. Daily application of the marine oil to open wounds made by punch biopsy in db/db mice promoted wound closure by accelerating the resolution of inflammation, inducing neoangiogenesis and M¿1/M¿2 macrophage polarization. In conclusion, LIPINOVA® displays pro-resolutive properties and could be exploited as a therapeutic agent for the treatment of diabetic ulcers.
  • Autores: Montero Calle, Maria del Pilar; Flandes Iparraguirre, María; Mountris, K.; et al.
    Revista: BIOFABRICATION
    ISSN: 1758-5082 Vol.14 N° 4 2022 págs. 045017
    Resumen
    Biofabrication of human tissues has seen a meteoric growth triggered by recent technical advancements such as human induced pluripotent stem cells (hiPSCs) and additive manufacturing. However, generation of cardiac tissue is still hampered by lack of adequate mechanical properties and crucially by the often unpredictable post-fabrication evolution of biological components. In this study we employ melt electrowriting (MEW) and hiPSC-derived cardiac cells to generate fibre-reinforced human cardiac minitissues. These are thoroughly characterized in order to build computational models and simulations able to predict their post-fabrication evolution. Our results show that MEW-based human minitissues display advanced maturation 28 post-generation, with a significant increase in the expression of cardiac genes such as MYL2, GJA5, SCN5A and the MYH7/MYH6 and MYL2/MYL7 ratios. Human iPSC-cardiomyocytes are significantly more aligned within the MEW-based 3D tissues, as compared to conventional 2D controls, and also display greater expression of C x43. These are also correlated with a more mature functionality in the form of faster conduction velocity. We used these data to develop simulations capable of accurately reproducing the experimental performance. In-depth gauging of the structural disposition (cellular alignment) and intercellular connectivity (C x43) allowed us to develop an improved computational model able to predict the relationship between cardiac cell alignment and functional performance. This study lays down the path for advancing in the development of in silico tools to predict cardiac biofabricated tissue evolution after generation, and maps the route towards more accurate and biomimetic tissue manufacture.
  • Autores: Lamo de Espinosa Vázquez de Sola, José María (Autor de correspondencia); Alfonso, A.; Pascual, E.; et al.
    Revista: DIAGNOSTICS
    ISSN: 2075-4418 Vol.12 N° 5 2022 págs. 1128
    Resumen
    Objective: The aim of the study is to describe the morphology associated with the development of osteoarthritis (OA) in three different age groups. These data will contribute to defining the morphology associated with early and late hip OA. Methods: We studied 400 hips in 377 patients who had undergone primary THA due to idiopathic OA. Three groups were compared: group 1 (n = 147), younger patients, aged up to 60 years; group 2 (n = 155), patients aged between 61 and 74 years; and group 3 (n = 98), aged 75 or over. Five independent researchers measured the hip angles and the mean values were used to build a database. Results: No differences between groups in sex distribution and BMI were detected. Less coverage of the head (extrusion index), higher Tonnis angle, lower Wiberg and alpha angles characterized early OA hips. These differences increased with age, being greater between group 2 and group 3 (p < 0.01). However, significant differences were still present in the comparison between group 1 and group 2 (p < 0.01)). No differences were detected between group 2 and group 3. Conclusion: Elevated acetabular angle, head extrusion and decreased Wiberg angle characterize hip osteoarthritis at younger ages and should be the focus of hip preservation surgery in terms of osteoarthritis prevention. Pincer-type FAI (higher Wiberg and lower Tonnis angle) and higher alpha angle (CAM) are correlated with the development of later OA. These results shed doubt on applying the hip preservation surgery concept in terms of osteoarthritis prevention in FAI, especially in Pincer-type FAI patients.
  • Autores: Gil-Melgosa, L.; Grasa, J.; Urbiola, A.; et al.
    Revista: BIOMEDICINES
    ISSN: 2227-9059 Vol.10 N° 1 2022 págs. 19
    Resumen
    Achilles tendon rupture is a frequent injury with an increasing incidence. After clinical surgical repair, aimed at suturing the tendon stumps back into their original position, the repaired Achilles tendon is often plastically deformed and mechanically less strong than the pre-injured tissue, with muscle fatty degeneration contributing to function loss. Despite clinical outcomes, pre-clinical research has mainly focused on tendon structural repair, with a lack of knowledge regarding injury progression from tendon to muscle and its consequences on muscle degenerative/regenerative processes and function. Here, we characterize the morphological changes in the tendon, the myotendinous junction and muscle belly in a mouse model of Achilles tendon complete rupture, finding cellular and fatty infiltration, fibrotic tissue accumulation, muscle stem cell decline and collagen fiber disorganization. We use novel imaging technologies to accurately relate structural alterations in tendon fibers to pathological changes, which further explain the loss of muscle mechanical function after tendon rupture. The treatment of tendon injuries remains a challenge for orthopedics. Thus, the main goal of this study is to bridge the gap between clinicians' knowledge and research to address the underlying pathophysiology of ruptured Achilles tendon and its consequences in the gastrocnemius. Such studies are necessary if current practices in regenerative medicine for Achilles tendon ruptures are to be improved.
  • Autores: López Muneta, Leyre; Linares Acosta, Javier; Casis, O.; et al.
    Revista: FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
    ISSN: 2296-634X Vol.9 2022 págs. 797927
    Resumen
    Direct cardiac reprogramming has emerged as an interesting approach for the treatment and regeneration of damaged hearts through the direct conversion of fibroblasts into cardiomyocytes or cardiovascular progenitors. However, in studies with human cells, the lack of reporter fibroblasts has hindered the screening of factors and consequently, the development of robust direct cardiac reprogramming protocols.In this study, we have generated functional human NKX2.5(GFP) reporter cardiac fibroblasts. We first established a new NKX2.5(GFP) reporter human induced pluripotent stem cell (hiPSC) line using a CRISPR-Cas9-based knock-in approach in order to preserve function which could alter the biology of the cells. The reporter was found to faithfully track NKX2.5 expressing cells in differentiated NKX2.5(GFP) hiPSC and the potential of NKX2.5-GFP + cells to give rise to the expected cardiac lineages, including functional ventricular- and atrial-like cardiomyocytes, was demonstrated. Then NKX2.5(GFP) cardiac fibroblasts were obtained through directed differentiation, and these showed typical fibroblast-like morphology, a specific marker expression profile and, more importantly, functionality similar to patient-derived cardiac fibroblasts. The advantage of using this approach is that it offers an unlimited supply of cellular models for research in cardiac reprogramming, and since NKX2.5 is expressed not only in cardiomyocytes but also in cardiovascular precursors, the detection of both induced cell types would be possible. These reporter lines will be useful tools for human direct cardiac reprogramming research and progress in this field.
  • Autores: Urtaza, U. (Autor de correspondencia); Guaresti, O.; Gorronogoitia, I.; et al.
    Revista: BIOMEDICAL MATERIALS
    ISSN: 1748-6041 Vol.17 N° 4 2022 págs. 045028
    Resumen
    This work identifies and describes different material-scaffold geometry combinations for cartilage tissue engineering (CTE). Previously reported potentially interesting scaffold geometries were tuned and printed using bioresorbable polycaprolactone and poly(lactide-b-ethylene) block copolymer. Medical grades of both polymers were 3D printed with fused filament fabrication technology within an ISO 7 classified cleanroom. Resulting scaffolds were then optically, mechanically and biologically tested. Results indicated that a few material-scaffold geometry combinations present potential for excellent cell viability as well as for an enhance of the chondrogenic properties of the cells, hence suggesting their suitability for CTE applications.
  • Autores: Moya Jodar, Marta; Coppiello, Giulia; Rodríguez Madoz, Juan Roberto; et al.
    Revista: ANIMALS
    ISSN: 2076-2615 Vol.12 N° 14 2022 págs. 1829
    Resumen
    Simple Summary One of the latest goals in regenerative medicine is to use pluripotent stem cells to generate whole organs in vivo through the blastocyst complementation technique. This method consists of the microinjection of pluripotent stem cells into preimplantation embryos that have been genetically modified to ablate the development of a target organ. By taking advantage of the spatiotemporal clues present in the developing embryo, pluripotent stem cells are able to colonize the empty developmental niche and create the missing organ. Combining human pluripotent stem cells with genetically engineered pig embryos, it would be possible to obtain humanized organs that could be used for transplantation, and, therefore, solve the worldwide issue of insufficient availability of transplantable organs. As endothelial cells play a critical role in xenotransplantation rejection in all organs, in this study, we optimized a protocol to generate a vascular-disabled preimplantation pig embryo using the CRISPR/Cas9 system. This protocol could be used to generate avascular embryos for blastocyst complementation experiments and work towards the generation of rejection-free humanized organs in pigs. Each year, tens of thousands of people worldwide die of end-stage organ failure due to the limited availability of organs for use in transplantation. To meet this clinical demand, one of the last frontiers of regenerative medicine is the generation of humanized organs in pigs from pluripotent stem cells (PSCs) via blastocyst complementation. For this, organ-disabled pig models are needed. As endothelial cells (ECs) play a critical role in xenotransplantation rejection in every organ, we aimed to produce hematoendothelial-disabled pig embryos targeting the master transcription factor ETV2 via CRISPR-Cas9-mediated genome modification. In this study, we designed five different guide RNAs (gRNAs) against the DNA-binding domain of the porcine ETV2 gene, which were tested on porcine fibroblasts in vitro. Four out of five guides showed cleavage capacity and, subsequently, these four guides were microinjected individually as ribonucleoprotein complexes (RNPs) into one-cell-stage porcine embryos. Next, we combined the two gRNAs that showed the highest targeting efficiency and microinjected them at higher concentrations. Under these conditions, we significantly improved the rate of biallelic mutation. Hence, here, we describe an efficient one-step method for the generation of hematoendothelial-disabled pig embryos via CRISPR-Cas9 microinjection in zygotes. This model could be used in experimentation related to the in vivo generation of humanized organs.
  • Autores: Pérez Estenaga, Íñigo; Chevalier, M. T.; Pena, E.; et al.
    Revista: EUROPEAN JOURNAL OF HEART FAILURE
    ISSN: 1388-9842 Vol.24 N° Suppl. 2 2022 págs. 43 - 44
  • Autores: Mazo Vega, Manuel María; Montero Calle, Maria del Pilar; Flandes Iparraguirre, María; et al.
    Revista: TISSUE ENGINEERING PART A
    ISSN: 1937-3341 Vol.28 N° Supl. 1 2022 págs. S129
  • Autores: Ozkan, H.; Valdés Fernández, José; Willcockson, H. H.; et al.
    Revista: OSTEOARTHRITIS AND CARTILAGE
    ISSN: 1063-4584 Vol.30 N° Suppl. 1 2022 págs. S293 - S294
  • Autores: Moya-Garzón, M. D.; Gómez-Vidal, J. A.; Alejo-Armijo, A.; et al.
    Revista: JOURNAL OF PERSONALIZED MEDICINE
    ISSN: 2075-4426 Vol.11 N° 2 2021 págs. 74
    Resumen
    Primary hyperoxalurias (PHs) are a group of inherited alterations of the hepatic glyoxylate metabolism. PHs classification based on gene mutations parallel a variety of enzymatic defects, and all involve the harmful accumulation of calcium oxalate crystals that produce systemic damage. These geographically widespread rare diseases have a deep impact in the life quality of the patients. Until recently, treatments were limited to palliative measures and kidney/liver transplants in the most severe forms. Efforts made to develop pharmacological treatments succeeded with the biotechnological agent lumasiran, a siRNA product against glycolate oxidase, which has become the first effective therapy to treat PH1. However, small molecule drugs have classically been preferred since they benefit from experience and have better pharmacological properties. The development of small molecule inhibitors designed against key enzymes of glyoxylate metabolism is on the focus of research. Enzyme inhibitors are successful and widely used in several diseases and their pharmacokinetic advantages are well known. In PHs, effective enzymatic targets have been determined and characterized for drug design and interesting inhibitory activities have been achieved both in vitro and in vivo. This review describes the most recent advances towards the development of small molecule enzyme inhibitors in the treatment of PHs, introducing the multi-target approach as a more effective and safe therapeutic option.
  • Autores: Tadevosyan, K.; Iglesias García, Olalla (Autor de correspondencia); Mazo Vega, Manuel María; et al.
    Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
    ISSN: 1422-0067 Vol.22 N° 3 2021 págs. 1479
    Resumen
    Cardiac tissue engineering is very much in a current focus of regenerative medicine research as it represents a promising strategy for cardiac disease modelling, cardiotoxicity testing and cardiovascular repair. Advances in this field over the last two decades have enabled the generation of human engineered cardiac tissue constructs with progressively increased functional capabilities. However, reproducing tissue-like properties is still a pending issue, as constructs generated to date remain immature relative to native adult heart. Moreover, there is a high degree of heterogeneity in the methodologies used to assess the functionality and cardiac maturation state of engineered cardiac tissue constructs, which further complicates the comparison of constructs generated in different ways. Here, we present an overview of the general approaches developed to generate functional cardiac tissues, discussing the different cell sources, biomaterials, and types of engineering strategies utilized to date. Moreover, we discuss the main functional assays used to evaluate the cardiac maturation state of the constructs, both at the cellular and the tissue levels. We trust that researchers interested in developing engineered cardiac tissue constructs will find the information reviewed here useful. Furthermore, we believe that providing a unified framework for comparison will further the development of human engineered cardiac tissue constructs displaying the specific properties best suited for each particular application.
  • Autores: Lamo de Espinosa Vázquez de Sola, José María; Prosper Cardoso, Felipe; Blanco, J. F.; et al.
    Revista: JOURNAL OF TRANSLATIONAL MEDICINE
    ISSN: 1479-5876 Vol.19 N° 1 2021 págs. 506
    Resumen
    Knee osteoarthritis is the most prevalent joint disease and a frequent cause of pain, functional loss and disability. Conventional treatments have demonstrated only modest clinical benefits whereas cell-based therapies have shown encouraging results, but important details, such as dose needed, long-term evolution or number of applications required are scarcely known. Here we have reanalyzed results from two recent pilot trials with autologous bone marrow-derived mesenchymal stromal cells using the Huskisson plot to enhance quantification of efficacy and comparability. We find that cell doses of 10, 40 and 100 million autologous cells per knee provided quite similar healing results and that much of the effect attained 1 year after cell application remained after 2 and 4 years. These results are encouraging because they indicate that, apart from safety and simplicity: (i) the beneficial effect is both significant and sizeable, (ii) it can be achieved with a single injection of cells, and (iii) the effect is perdurable for years.
  • Autores: Valdés Fernández, José (Autor de correspondencia); López-Martínez, T.; Ripalda Cemborain, Purificación; et al.
    Revista: JOURNAL OF BONE AND MINERAL RESEARCH
    ISSN: 0884-0431 Vol.36 N° 11 2021 págs. 2203 - 2213
    Resumen
    The remodeling of the extracellular matrix is a central function in endochondral ossification and bone homeostasis. During secondary fracture healing, vascular invasion and bone growth requires the removal of the cartilage intermediate and the coordinate action of the collagenase matrix metalloproteinase (MMP)-13, produced by hypertrophic chondrocytes, and the gelatinase MMP-9, produced by cells of hematopoietic lineage. Interfering with these MMP activities results in impaired fracture healing characterized by cartilage accumulation and delayed vascularization. MMP-10, Stromelysin 2, a matrix metalloproteinase with high homology to MMP-3 (Stromelysin 1), presents a wide range of putative substrates identified in vitro, but its targets and functions in vivo and especially during fracture healing and bone homeostasis are not well defined. Here, we investigated the role of MMP-10 through bone regeneration in C57BL/6 mice. During secondary fracture healing, MMP-10 is expressed by hematopoietic cells and its maximum expression peak is associated with cartilage resorption at 14 days post fracture (dpf). In accordance with this expression pattern, when Mmp10 is globally silenced, we observed an impaired fracture-healing phenotype at 14 dpf, characterized by delayed cartilage resorption and TRAP-positive cell accumulation. This phenotype can be rescued by a non-competitive transplant of wild-type bone marrow, indicating that MMP-10 functions are required only in cells of hematopoietic linage. In addition, we found that this phenotype is a consequence of reduced gelatinase activity and the lack of proMMP-9 processing in macrophages. Our data provide evidence of the in vivo function of MMP-10 during endochondral ossification and defines the macrophages as the lead cell population in cartilage removal and vascular invasion. (c) 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
  • Autores: López Díaz de Cerio, Ascensión; Pérez Estenaga, Íñigo; Inoges Sancho, Susana Inmaculada; et al.
    Revista: PHARMACEUTICS
    ISSN: 1999-4923 Vol.13 N° 8 2021 págs. 1269
    Resumen
    The use of allogeneic adipose-derived mesenchymal stromal cells (alloADSCs) represents an attractive approach for treating myocardial infarction (MI). Furthermore, adding a natural support improves alloADSCs engraftment and survival in heart tissues, leading to a greater therapeutic effect. We aimed to examine the safety and immunological reaction induced by epicardial implantation of a clinical-grade collagen scaffold (CS) seeded with alloADSCs for its future application in humans. Thus, cellularized scaffolds were myocardially or subcutaneously implanted in immunosuppressed rodent models. The toxicological parameters were not significantly altered, and tumor formation was not found over the short or long term. Furthermore, biodistribution analyses in the infarcted immunocompetent rats displayed cell engraftment in the myocardium but no migration to other organs. The immunogenicity of alloADSC-CS was also evaluated in a preclinical porcine model of chronic MI; no significant humoral or cellular alloreactive responses were found. Moreover, CS cellularized with human ADSCs cocultured with human allogeneic immune cells produced no alloreactive response. Interestingly, alloADSC-CS significantly inhibited lymphocyte responses, confirming its immunomodulatory action. Thus, alloADSC-CS is likely safe and does not elicit any alloreactive immunological response in the host. Moreover, it exerts an immunomodulatory action, which supports its translation to a clinical setting.
  • Autores: Vera Álvarez, Laura; García Olloqui, Paula; Petri González, Eva; et al.
    Revista: AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
    ISSN: 1044-1549 Vol.64 N° 4 2021 págs. 465 - 476
    Resumen
    Fibroblast activation includes differentiation to myofibroblasts and is a key feature of organ fibrosis. The Notch pathway has been involved in myofibroblast differentiation in several tissues, including the lung. Here, we identify a subset of collagen-expressing cells in the lung that exhibit Notch3 activity at homeostasis. After injury, this activation increases, being found in alpha SMA-expressing myofibroblasts in the mouse and human fibrotic lung. Although previous studies suggest a contribution of Notch3 in stromal activation, in vivo evidence of the role of Notch3 in lung fibrosis remains unknown. In this study, we examine the effects of Notch3 deletion in pulmonary fibrosis and demonstrate that Notch3-deficient lungs are protected from lung injury with significantly reduced collagen deposition after bleomycin administration. The induction of profibrotic genes is reduced in bleomycin-treated Notch3-knockout lungs that consistently present fewer alpha SMA-positive myofibroblasts. As a result, the volume of healthy lung tissue is higher and lung function is improved in the absence of Notch3. Using in vitro cultures of lung primary fibroblasts, we confirmed that Notch3 participates in their survival and differentiation. Thus, Notch3 deficiency mitigates the development of lung fibrosis because of its role in mediating fibroblast activation. Our findings reveal a previously unidentified mechanism underlying lung fibrogenesis and provide a potential novel therapeutic approach to target pulmonary fibrosis.
  • Autores: Torres, A. G.; Rodríguez-Escribà, M.; Marcet-Houben, M.; et al.
    Revista: NUCLEIC ACIDS RESEARCH
    ISSN: 0305-1048 Vol.49 N° 12 2021 págs. 7011 - 7034
    Resumen
    The modification of adenosine to inosine at the wobble position (134) of tRNA anticodons is an abundant and essential feature of eukaryotic tRNAs. The expansion of inosine-containing tRNAs in eukaryotes followed the transformation of the homodimeric bacterial enzyme TadA, which generates 134 in tRNA(Arg) and tRNA(Leu), into the heterodimeric eukaryotic enzyme ADAT, which modifies up to eight different tRNAs. The emergence of ADAT and its larger set of substrates, strongly influenced the tRNA composition and codon usage of eukaryotic genomes. However, the selective advantages that drove the expansion of 134-tRNAs remain unknown. Here we investigate the functional relevance of 134-tRNAs in human cells and show that a full complement of these tRNAs is necessary for the translation of low-complexity protein domains enriched in amino acids cognate for 134-tRNAs. The coding sequences for these domains require codons translated by 134-tRNAs, in detriment of synonymous codons that use other tRNAs. 134-tRNA-dependent low-complexity proteins are enriched in functional categories related to cell adhesion, and depletion in 134-tRNAs leads to cellular phenotypes consistent with these roles. We show that the distribution of these low-complexity proteins mirrors the distribution of 134-tRNAs in the phylogenetic tree.
  • Autores: Abizanda Sarasa, Gloria María; López Muneta, Leyre; Linares Acosta, Javier; et al.
    Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
    ISSN: 1422-0067 Vol.22 N° 17 2021 págs. 9126
    Resumen
    The success of cell therapy for the treatment of myocardial infarction depends on finding novel approaches that can substantially implement the engraftment of the transplanted cells. In order to enhance cell engraftment, most studies have focused on the pretreatment of transplantable cells. Here we have considered an alternative approach that involves the preconditioning of infarcted heart tissue to reduce endogenous cell activity and thus provide an advantage to our exogenous cells. This treatment is routinely used in other tissues such as bone marrow and skeletal muscle to improve cell engraftment, but it has never been taken in cardiac tissue. To avoid long-term cardiotoxicity induced by full heart irradiation we developed a rat model of a catheter-based heart irradiation system to locally impact a delimited region of the infarcted cardiac tissue. As proof of concept, we transferred ZsGreen(+) iPSCs in the infarcted heart, due to their ease of use and detection. We found a very significant increase in cell engraftment in preirradiated rats. In this study, we demonstrate for the first time that preconditioning the infarcted cardiac tissue with local irradiation can substantially enhance cell engraftment.
  • Autores: Baraibar Churio, Arantxa; Bobadilla Muñoz, Miriam; Machado, F. J. D.; et al.
    Revista: LIFE
    ISSN: 2075-1729 Vol.11 N° 12 2021 págs. 1398
    Resumen
    Matrix metalloproteinases (MMPs) have been implicated in the progression of muscular dystrophy, and recent studies have reported the role of MMP-10 in skeletal muscle pathology of young dystrophic mice. Nevertheless, its involvement in dystrophin-deficient hearts remains unexplored. Here, we aimed to investigate the involvement of MMP-10 in the progression of severe muscular dystrophy and to characterize MMP-10 loss in skeletal and cardiac muscles of aged dystrophic mice. We examined the histopathological effect of MMP-10 ablation in aged mdx mice, both in the hind limb muscles and heart tissues. We found that MMP-10 loss compromises survival rates of aged mdx mice, with skeletal and cardiac muscles developing a chronic inflammatory response. Our findings indicate that MMP-10 is implicated in severe muscular dystrophy progression, thus identifying a new area of research that could lead to future therapies for dystrophic muscles.
  • Autores: Yañez Arauz, J. M.; Yañez Arauz, J. M.; Montiel Terrón, Veronica; et al.
    Revista: REVISTA DE LA ASOCIACION ARGENTINA DE ORTOPEDIA Y TRAUMATOLOGIA
    ISSN: 1515-1786 Vol.86 N° 2 2021 págs. 139 - 150
    Resumen
    Introducción: Las técnicas para corregir las deformidades del hallux incluyen osteotomías metatarsianas y falángicas. Las osteotomías sobre la falange proximal corrigen el DASA y el ángulo interfalángico. Sin embargo, no se han publicado las indicaciones para la osteotomía de la falange distal. El objetivo de este artículo es comunicar la técnica y las indicaciones de la osteotomía percutánea de la falange distal del hallux, y evaluar los resultados de una serie de casos. Materiales y Métodos: Se analizaron 14 pies en los que se realizó una osteotomía de la falange distal del hallux para corregir una deformidad. Se midieron el DASA, la oblicuidad interfalángica y el ángulo falange distal-interfalángico en las radiografías. La técnica quirúrgica fue percutánea con control fluoroscópico. Los resultados se evaluaron mediante las escalas analógica visual de dolor y AOFAS. Seguimiento medio: 52 meses. Resultados: 13 pies de mujeres y un pie de hombre. Edad promedio: 58 años. Los resultados clínico y estético fueron excelentes, con alivio del dolor. Mejoría de la escala AOFAS: promedio 37 puntos. Análisis comparativo de ángulos preoperatorios y posoperatorios: DASA (p = 0,01), excepto cuando se aisló de la muestra a los pacientes con osteotomía tipo Akin (p = 0,33); ángulos F2-IF y F2-MTF (p <0,00001). Se registraron las complicaciones. Conclusiones: En la deformidad en valgo de la falange distal del hallux sintomática, se debe considerar una osteotomía correctora sola o asociada a osteotomía de la falange proximal. La osteotomía percutánea de la falange distal es un método eficaz, seguro y rápido. Nivel de Evidencia: IV
  • Autores: Montiel Terrón, Veronica (Autor de correspondencia); Vitoria Sola, María; Lamo de Espinosa Vázquez de Sola, José María; et al.
    Revista: ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY
    ISSN: 1434-3916 Vol.141 N° 2 2021 págs. 313 - 319
    Resumen
    Introduction The knee in Parkinson's disease (PD) patients is a problematic joint due to pain, stiffness and gait instability. The aim of this study is to evaluate the functional outcome and degree of pain relief achieved after total knee arthroplasty (TKA) in PD patients. Materials and methods This is a retrospective review of 26 PD patients (32 knees) with osteoarthritis who underwent a TKA between 1994 and 2013. Comorbidities, anesthetic procedures and complications were recorded. Patient functional status was assessed with the Knee Society Function Score (KFS) and the Knee Society Score (KSS). PD stage was classified with the Hoehn and Yahr Scale. Results The mean follow-up was 3.5 years (range 2-9). The mean age was 71 years (range 61-83) with a mean time since PD diagnosis of 11.8 years (range 4-24). PD severity on the Hoehn and Yahr Scale was 1.5 points before surgery and 2 points postoperatively. Pain on the visual analogic scale improved from 8 points preoperatively to 5 points at 1-year follow-up; function improved from 32 (range 20-45) to 71 (range 50-81) and from 34 (range 28-52) to 59 (range 25-76) on the KSS and KFS, respectively. The mean postoperative hospital stay was 9.8 days (range 5-21). Confusion and flexion contracture were the most frequent perioperative complications. Conclusion TKA successfully provided pain relief in PD patients. However, the functional outcome is related to disease progression and, therefore, variable. Perioperative complications are difficult to avoid and manage.
  • Autores: Perez-Prieto, D. (Autor de correspondencia); Perelli, S.; Corcoll, F. ; et al.
    Revista: INTERNATIONAL ORTHOPAEDICS
    ISSN: 0341-2695 Vol.45 N° 6 2021 págs. 1407 - 1411
    Resumen
    Purpose The main aim of this study was to evaluate the re-rupture risk after an anterior cruciate ligament reconstruction (ACL-R) using the vancomycin soaking technique and to compare it with the re-rupture risk in patients on whom this technique was not utilized. The secondary purpose was to compare the functional outcomes of those two subsets of patients operated on for ACL-R. The hypotheses are that the vancomycin soaking technique does not affect the re-rupture risk or the functional outcomes. Material and methods A retrospective historical cohort study was conducted. Two groups were compared in terms of the re-rupture rate (traumatic or atraumatic) and functional outcomes (International Knee Documentation Committee (IKDC), Tegner, and Lysholm). Group 1 consisted of patients that received pre-operative IV antibiotics. In group 2, the patients received pre-operative IV antibiotics along with a graft that had been presoaked in a vancomycin solution. A minimum follow-up of five years was required. Results There were 17 patients that suffered a re-rupture in group 1 (4.7%) and 15 in group 2 (3.9%) (n.s.). IKDC was 82.0 in group 1 and 83.9 in group 2 (p = 0.049); Tegner scored 4 in both groups (n.s.) and Lysholm was 90.3 in group 1 and 92.0 in group 2 (p = 0.015). Conclusion The vancomycin soaking technique for ACL autografts is a safe procedure for the daily clinical practice, in terms of re-ruptures. Moreover, it does not impair functional outcomes after an ACL-R.
  • Autores: Soria-Juan, B.; García-Arranz, M.; Jiménez, L. L.; et al.
    Revista: TRIALS
    ISSN: 1745-6215 Vol.22 N° 1 2021 págs. 595
    Resumen
    Background: Chronic lower limb ischemia develops earlier and more frequently in patients with type 2 diabetes mellitus. Diabetes remains the main cause of lower-extremity non-traumatic amputations. Current medical treatment, based on antiplatelet therapy and statins, has demonstrated deficient improvement of the disease. In recent years, research has shown that it is possible to improve tissue perfusion through therapeutic angiogenesis. Both in animal models and humans, it has been shown that cell therapy can induce therapeutic angiogenesis, making mesenchymal stromal cell-based therapy one of the most promising therapeutic alternatives. The aim of this study is to evaluate the feasibility, safety, and efficacy of cell therapy based on mesenchymal stromal cells derived from adipose tissue intramuscular administration to patients with type 2 diabetes mellitus with critical limb ischemia and without possibility of revascularization. Methods: A multicenter, randomized double-blind, placebo-controlled trial has been designed. Ninety eligible patients will be randomly assigned at a ratio 1:1:1 to one of the following: control group (n = 30), low-cell dose treatment group (n = 30), and high-cell dose treatment group (n = 30). Treatment will be administered in a single-dose way and patients will be followed for 12 months. Primary outcome (safety) will be evaluated by measuring the rate of adverse events within the study period. Secondary outcomes (efficacy) will be measured by assessing clinical, analytical, and imaging-test parameters. Tertiary outcome (quality of life) will be evaluated with SF-12 and VascuQol-6 scales. Discussion: Chronic lower limb ischemia has limited therapeutic options and constitutes a public health problem in both developed and underdeveloped countries. Given that the current treatment is not established in daily clinical practice, it is essential to provide evidence-based data that allow taking a step forward in its clinical development. Also, the multidisciplinary coordination exercise needed to develop this clinical trial protocol will undoubtfully be useful to conduct academic clinical trials in the field of cell therapy in the near future.
  • Autores: Sáenz Idoate, Víctor; Salterain González, Nahikari; Torres Santamaría, María José; et al.
    Revista: EUROPEAN JOURNAL OF HEART FAILURE
    ISSN: 1388-9842 Vol.23 N° Supl. 2 2021 págs. 29 - 30
  • Autores: Calviño Sampedro, Cristina; Ceballos, C.; Inoges Sancho, Susana Inmaculada; et al.
    Revista: HUMAN GENE THERAPY
    ISSN: 1043-0342 Vol.32 N° 19-20 2021 págs. A36 - A37
  • Autores: Salterain González, Nahikari; Ibero Valencia, Javier; Riesgo García, Álvaro; et al.
    Revista: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
    ISSN: 0735-1097 Vol.77 N° 18 Supl. 1 2021 págs. 854 - 854
  • Autores: Molinos-Vicente, A.; García-Torralba, A.; Nieto-Romero, V.; et al.
    Revista: MOLECULAR THERAPY
    ISSN: 1525-0016 Vol.29 N° 4 2021 págs. 246 - 246
  • Autores: Wu, M.; Claus, P.; De Buck, S.; et al.
    Revista: EUROPEAN HEART JOURNAL
    ISSN: 0195-668X Vol.42 N° Supl. 1 2021 págs. 912
  • Autores: Reverter, E.; Juanola, A.; Prado, V.; et al.
    Revista: JOURNAL OF HEPATOLOGY (ONLINE)
    ISSN: 0168-8278 Vol.75 N° Supl. 2 2021 págs. S329 - S330
  • Autores: Tamayo, L.; Tamayo Uria, Ibon; Vales Aranguren, África; et al.
    Revista: JOURNAL OF HEPATOLOGY (ONLINE)
    ISSN: 0168-8278 Vol.75 N° Supl. 2 2021 págs. S694 - S694
  • Autores: Díaz Mazquiaran, Aintzane; de la Fuente Cedeño, J.; SERRANO SANZ, Guillermo; et al.
    Revista: HAEMATOLOGICA
    ISSN: 0390-6078 Vol.106 N° 10 s2 2021 págs. 100 - 101
  • Autores: Montero Calle, Maria del Pilar; Flandes Iparraguirre, María; Musquiz, S.; et al.
    Revista: ECLINICALMEDICINE
    ISSN: 2589-5370 Vol.8 2020 págs. 955
    Resumen
    Cardiovascular disease is the number one killer worldwide, with myocardial infarction (MI) responsible for approximately 1 in 6 deaths. The lack of endogenous regenerative capacity, added to the deleterious remodelling programme set into motion by myocardial necrosis, turns MI into a progressively debilitating disease, which current pharmacological therapy cannot halt. The advent of Regenerative Therapies over 2 decades ago kick-started a whole new scientific field whose aim was to prevent or even reverse the pathological processes of MI. As a highly dynamic organ, the heart displays a tight association between 3D structure and function, with the non-cellular components, mainly the cardiac extracellular matrix (ECM), playing both fundamental active and passive roles. Tissue engineering aims to reproduce this tissue architecture and function in order to fabricate replicas able to mimic or even substitute damaged organs. Recent advances in cell reprogramming and refinement of methods for additive manufacturing have played a critical role in the development of clinically relevant engineered cardiovascular tissues. This review focuses on the generation of human cardiac tissues for therapy, paying special attention to human pluripotent stem cells and their derivatives. We provide a perspective on progress in regenerative medicine from the early stages of cell therapy to the present day, as well as an overview of cellular processes, materials and fabrication strategies currently under investigation. Finally, we summarise current clinical applications and reflect on the most urgent needs and gaps to be filled for efficient translation to the clinical arena.
  • Autores: López Muneta, Leyre; Miranda-Arrubla, J.; Carvajal Vergara, Xonia (Autor de correspondencia)
    Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
    ISSN: 1422-0067 Vol.21 N° 21 2020 págs. 7950
    Resumen
    Direct cardiac reprogramming has emerged as a novel therapeutic approach to treat and regenerate injured hearts through the direct conversion of fibroblasts into cardiac cells. Most studies have focused on the reprogramming of fibroblasts into induced cardiomyocytes (iCMs). The first study in which this technology was described, showed that at least a combination of three transcription factors, GATA4, MEF2C and TBX5 (GMT cocktail), was required for the reprogramming into iCMs in vitro using mouse cells. However, this was later demonstrated to be insufficient for the reprogramming of human cells and additional factors were required. Thereafter, most studies have focused on implementing reprogramming efficiency and obtaining fully reprogrammed and functional iCMs, by the incorporation of other transcription factors, microRNAs or small molecules to the original GMT cocktail. In this respect, great advances have been made in recent years. However, there is still no consensus on which of these GMT-based varieties is best, and robust and highly reproducible protocols are still urgently required, especially in the case of human cells. On the other hand, apart from CMs, other cells such as endothelial and smooth muscle cells to form new blood vessels will be fundamental for the correct reconstruction of damaged cardiac tissue. With this aim, several studies have centered on the direct reprogramming of fibroblasts into induced cardiac progenitor cells (iCPCs) able to give rise to all myocardial cell lineages. Especially interesting are reports in which multipotent and highly expandable mouse iCPCs have been obtained, suggesting that clinically relevant amounts of these cells could be created. However, as of yet, this has not been achieved with human iCPCs, and exactly what stage of maturity is appropriate for a cell therapy product remains an open question. Nonetheless, the major concern in regenerative medicine is the poor retention, survival, and engraftment of transplanted cells in the cardiac tissue. To circumvent this issue, several cell pre-conditioning approaches are currently being explored. As an alternative to cell injection, in vivo reprogramming may face fewer barriers for its translation to the clinic. This approach has achieved better results in terms of efficiency and iCMs maturity in mouse models, indicating that the heart environment can favor this process. In this context, in recent years some studies have focused on the development of safer delivery systems such as Sendai virus, Adenovirus, chemical cocktails or nanoparticles. This article provides an in-depth review of the in vitro and in vivo cardiac reprograming technology used in mouse and human cells to obtain iCMs and iCPCs, and discusses what challenges still lie ahead and what hurdles are to be overcome before results from this field can be transferred to the clinical settings.
  • Autores: Garcia-Olloqui, P.; Rodríguez Madoz, Juan Roberto; Di Scala, M. ; et al.
    Revista: JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
    ISSN: 1932-6254 Vol.14 N° 1 2020 págs. 123 - 134
    Resumen
    Adeno-associated viruses (AAV) have become one of the most promising tools for gene transfer in clinics. Among all the serotypes, AAV9 has been described as the most efficient for cardiac transduction. In order to achieve optimal therapeutic delivery in heart disease, we have explored AAV9 transduction efficiency in an infarcted heart using different routes of administration and promoters, including a cardiac-specific one. AAV9 vectors carrying luciferase or green fluorescence protein under the control of the ubiquitous elongation-factor-1-alpha or the cardiac-specific troponin-T (TnT) promoters were administered by intramyocardial or intravenous injection, either in healthy or myocardial-infarcted mice. The transduction efficacy and specificity, the time-course expression, and the safety of each vector were tested. High transgene expression levels were found in the heart, but not in the liver, of mice receiving AAV-TnT, which was significantly higher after intramyocardial injection regardless of ischemia-induction. On the contrary, high hepatic transgene expression levels were detected with the elongation-factor-1-alpha-promoter, independently of the administration route and heart damage. Moreover, tissue-specific green fluorescence protein expression was found in cardiomyocytes with the TnT vector, whereas minimal cardiac expression was detected with the ubiquitous one. Interestingly, we found that myocardial infarction greatly increased the transcriptional activity of AAV genomes. Our findings show that the use of cardiac promoters allows for specific and stable cardiac gene expression, which is optimal and robust when intramyocardially injected. Furthermore, our data indicate that the pathological status of the tissue can alter the transcriptional activity of AAV genomes, an aspect that should be carefully evaluated for clinical applications.
  • Autores: Nandi, R.; Yucknovsky, A.; Mazo Vega, Manuel María; et al.
    Revista: JOURNAL OF MATERIALS CHEMISTRY B
    ISSN: 2050-750X Vol.8 N° 31 2020 págs. 6964 - 6974
    Resumen
    Hydrogels are common platforms for drug delivery applications. Amongst the different loading and release methodologies, physisorption loading and passive release stand out for their straightforwardness. However, evaluating the inner environment and the surface of the polymer can be complicated, as they can be very different from the properties of the monomer composing the hydrogel. Here, we explore the inner environment of macroscopic bovine serum albumin (BSA) hydrogels, by using both the native Trp residues of the protein and the pyranine photoacid as fluorescent probes. Time-resolved fluorescence is used to follow the fast solvation dynamics of Trp and the excited-state proton dissociation of pyranine. The results show that upon gelation, the surface of the BSA within the hydrogel is less accessible to water,i.e., more hydrophobic, as compared to before gelation. This understanding is used to rationalize the different drug binding efficiencies of the anti-cancer drug doxorubicin to the hydrogel at different pH values, which changes the charge of the molecule. Finally, we give proof for the hydrogels capacity to effectively function as drug-carrier systemsin vitro, using different cancer cell lines over a 7 day period. Our study shows that relatively simple spectroscopic measurements can result in a fundamental structural and chemical understanding of (protein) hydrogels. From an application point of view, our protein hydrogels are very easy to form, without any need of complex chemical modification, they are very low cost as compared to other hydrogels, and show slow and sustained drug release profiles, all very sought-after properties.
  • Autores: Gil Melgosa, Lara; Valentí Azcárate, Andrés; Suárez López del Amo, Álvaro; et al.
    Revista: KNEE
    ISSN: 0968-0160 Vol.27 N° 5 2020 págs. 1585 - 1592
    Resumen
    Background: There is some controversy about how the proximal tibiofibular joint (PTFJ) capsulotomy changes PTFJ anatomy in closed-wedge high tibial osteotomy (CW-HTO) and about how this affects ankle and knee mobility and the onset of lateral knee pain. The aim of this study is to evaluate changes in PTFJ after CW-HTO, and its possible clinical significance. Methods: This study includes 50 patients who underwent CW-HTO with tibiofibular capsulotomy from 2000 to 2018 in our hospital. A clinical evaluation was conducted to evaluate pain location. The degrees of osteoarthritis and the proximal fibular subluxation were evaluated on radiographs. A dynamic analysis of the PTFJ was also performed comparing proximal fibular head subluxation on anteroposterior knee radiographs with the ankle placed in neutral position and dorsiflexed. Results: The clinical evaluation revealed that two patients had a sore scar, five had pain on the PTFJ with manual compression, and none referred lateral compartment pain. The radiological analysis revealed an average proximal subluxation of the fibular head after the osteotomy of 9.64 (range: 0-29) mm, which was greater in oblique PTFJ (p < 0.05). After the surgery, all the patients developed some degree of PTFJ arthritis. There was no correlation between lateral pain and proximal fibular subluxation, tibiofibular arthritis, or lateral compartment arthritis. The dynamic analysis revealed no significant changes. Conclusions: After CW-HTO all the patients developed proximal subluxation of the fibular head and a variable degree of PTFJ osteoarthritis, but these changes seem to be unrelated with lateral knee pain. (C) 2020 Elsevier B.V. All rights reserved.
  • Autores: Lamo de Espinosa Vázquez de Sola, José María (Autor de correspondencia); Blanco, J. F. ; Sanchez, M.; et al.
    Revista: JOURNAL OF TRANSLATIONAL MEDICINE
    ISSN: 1479-5876 Vol.18 N° 1 2020 págs. 356
    Resumen
    Background Mesenchymal stromal cells are a safe and promising option to treat knee osteoarthritis as previously demonstrated in different clinical trials. However, their efficacy, optimal dose and addition of adjuvants must be determined. Here, we evaluated the clinical effects of a dose of 100 x 10(6)bone marrow mesenchymal stromal cells (BM-MSCs) in combination with Platelet Rich Plasma (PRGF (R)) as adjuvant in a randomized clinical trial. Methods A phase II, multicenter, randomized clinical trial with active control was conducted. Sixty patients diagnosed with knee OA were randomly assigned to 3 weekly doses of PRGF (R) or intraarticular administration of 100 x 10(6)cultured autologous BM-MSCs plus PRGF (R). Patients were followed up for 12 months, and pain and function were assessed using VAS and WOMAC and by measuring the knee range of motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage. Results No adverse effects were reported after BM-MSC administration or during follow-up. According to VAS, the mean value (SD) for PRGF (R) and BM-MSC with PRGF (R) went from 5 (1.8) to 4.5 (2.2) (p = 0.389) and from 5.3 (1.9) to 3.5 (2.5) (p = 0.01), respectively at 12 months. In WOMAC, the mean (SD) baseline and 12-month overall WOMAC scores in patients treated with PRGF (R) was 31.9 (16.2) and 22.3 (15.8) respectively (p = 0.002) while that for patients treated with BM-MSC plus PRGF (R) was 33.4 (18.7) and 23.0 (16.6) (p = 0.053). Although statistical significances between groups have been not detected, only patients being treated with BM-MSC plus PRGF (R) could be considered as a OA treatment responders following OARSI criteria. X-ray and MRI (WORMS protocol) revealed no changes in knee joint space width or joint damage. Conclusions Treatment with BM-MSC associated with PRGF (R) was shown to be a viable therapeutic option for osteoarthritis of the knee, with clinical improvement at the end of follow-up. Further phase III clinical trials would be necessary to confirm the efficacy. Trial registrationClinical Trials.gov identifier NCT02365142. No EudraCT: 2011-006036-23
  • Autores: Montiel Terrón, Veronica (Autor de correspondencia); Troncoso Recio, Santiago; Valentí Azcárate, Andrés; et al.
    Revista: INDIAN JOURNAL OF ORTHOPAEDICS
    ISSN: 0019-5413 Vol.54 N° 6 2020 págs. 840 - 847
    Resumen
    Background During the last century, total hip arthroplasties have become more popular. They have had a huge impact on the quality of life, pain, range of motion, social interaction, and psychological well-being. A number of studies have emphasized the importance of using templates to choose the appropriate implant size when planning the surgery. Our aim is to use MediCad(R)software to analyze the ability of the digital template system MediCad(R)to predict the size of the implant needed in total hip arthroplasties. Materials and Methods An arthroplasty preoperative plan was created according to the MediCad(R)software guidelines, on anteroposterior hip X-ray by one junior resident, one senior resident, and three experienced hip surgeons. Results The median size accuracy was 0.7 (range: 0.27-0.87) for the cup, 0.73 (range: 0.36-0.83) for the stem, and 0.28 (range: -0.14-0.69) for the neck. Interobserver reliability was good (kappa > 0.4) and stronger when measuring the stem than when doing so with the cup. Conclusion: Digital preoperative total hip arthroplasty planning is a good method for predicting component size, restoring hip anatomy (vertical offset and horizontal offset), with good interobserver reliability.
  • Autores: Garcia-Arranz, M. (Autor de correspondencia); Garda-Olmo, D.; Herreros, M. D.; et al.
    Revista: STEM CELLS TRANSLATIONAL MEDICINE
    ISSN: 2157-6564 Vol.9 N° 3 2020 págs. 295 - 301
    Resumen
    The aim of this clinical trial (ID Number NCT01803347) was to determine the safety and efficacy of autologous adipose-derived stem cells (ASCs) for treatment of cryptoglandular fistula. This research was conducted following an analysis of the mistakes of a same previous phase III clinical trial. We designed a multicenter, randomized, single-blind clinical trial, recruiting 57 patients. Forty-four patients were categorized as belonging to the intent-to-treat group. Of these, 23 patients received 100 million ASCs plus intralesional fibrin glue (group A) and 21 received intralesional fibrin glue (group B), both after a deeper curettage of tracks and closure of internal openings. Fistula healing was defined as complete re-epithelialization of external openings. Those patients in whom the fistula had not healed after 16 weeks were eligible for retreatment. Patients were evaluated at 1, 4, 16, 36, and 52 weeks and 2 years after treatment. Results were assessed by an evaluator blinded to the type of treatment. After 16 weeks, the healing rate was 30.4% in group A and 42.8% in group B, rising to 55.0% and 63.1%, respectively, at 52 weeks. At the end of the study (2 years after treatment), the healing rate remained at 50.0% in group A and had reduced to 26.3% in group B. The safety of the cellular treatment was confirmed and no impact on fecal continence was detected. The main conclusion was that autologous ASCs for the treatment of cryptoglandular perianal fistula is safe and can favor long-term and sustained fistula healing.
  • Autores: Montiel Terrón, Veronica; Suárez López del Amo, Álvaro; Riera Alvarez, Luis; et al.
    Revista: INTERNATIONAL ORTHOPAEDICS
    ISSN: 0341-2695 Vol.44 N° 7 2020 págs. 1435 - 1439
    Resumen
    Background: Although different fixation techniques for the Akin osteotomy have been described in the literature, there are no many studies trying to analyze the differences between the types of fixation available. The aim of this study is to analyze if there are any differences between three types of staple fixation available in the market. Method: We present a retrospective study of 145 cases in which an Akin osteotomy was performed and fixed with three different kinds of implants staple A (28%), staple B (45%), and staple C (27%). Staple A is made out of stainless steel, and the surgeon mechanically controls the compression applied. Staple B increases the compression when heat is applied to it. Staple C has an intrinsic elastic memory that closes the osteotomy. In all cases, distal articular set angle, interphalangeal joint obliquity angle, and metatarsophalangeal angle were measured pre-operatively and 1.5 months post-operatively on dorsoplantar weight-bearing radiographs. Other details such as post-operative complications, implant migration, osteolysis, or fracture of the lateral cortex during surgery were also recorded. Results: Clinical and radiological results show no relevant differences between the three types of fixation. The mean angular corrections of DASA, interphalangeal joint obliquity angle, and metatarsophalangeal angle were 5, 12, and 21, respectively, for staple A; 4, 10, and 19, respectively, for staple B; and 7, 10, and 23, respectively, for staple C. The rates of intra-operative and post-operative complications were similar for all groups. There was one case of infection per group. We had five cases of delayed union two with staple A and three with staple C. In four cases, there was a loss of correction, two of them fixed with staple A and two with staple C. Seven cases developed a Südeck's syndrome, four of them fixed with staple A and three with staple C. Fifteen patients suffered an uncontrolled fracture of the lateral cortex of the phalanx when performing the osteotomy (3, 8, and 4 cases fixed with staples A, B, and C, respectively), and 87.5% of the patients that developed a plantar displacement of the osteotomy had an uncontrolled fracture of the lateral cortex (p < 0.05). All three staples achieved a rigid internal fixation and minimal periosteum damage and provided a good bone-bone contact. Conclusions: According to our results, the radiological differences are minimal, and although the thermal compression staple had less complication, clinical differences were also not statistically significant. This means the choice of implant could be left to the surgeon's preferences or made according to cost.
  • Autores: Marques, J.; Cortés Jiménez, Adriana; Pejenaute Martínez de Lizarrondo, Álvaro; et al.
    Revista: CELLS
    ISSN: 2073-4409 Vol.9 N° 3 2020 págs. 637
    Resumen
    Oxidative stress is a main molecular mechanism that underlies cardiovascular diseases. A close relationship between reactive oxygen species (ROS) derived from NADPH oxidase (NOX) activity and the prostaglandin (PG) biosynthesis pathway has been described. However, little information is available about the interaction between NOX5 homolog-derived ROS and the PG pathway in the cardiovascular context. Our main goal was to characterize NOX5-derived ROS effects in PG homeostasis and their potential relevance in cardiovascular pathologies. For that purpose, two experimental systems were employed: an adenoviral NOX5-beta overexpression model in immortalized human aortic endothelial cells (TeloHAEC) and a chronic infarction in vivo model developed from a conditional endothelial NOX5 knock-in mouse. NOX5 increased cyclooxygenase-2 isoform (COX-2) expression and prostaglandin E-2 (PGE(2)) production through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) in TeloHAEC. Protein kinase C (PKC) activation and intracellular calcium level (Ca++) mobilization increased ROS production and NOX5 overexpression, which promoted a COX-2/PGE(2) response in vitro. In the chronic infarction model, mice encoding endothelial NOX5 enhanced the cardiac mRNA expression of COX-2 and PGES, suggesting a COX-2/PGE(2) response to NOX5 presence in an ischemic situation. Our data support that NOX5-derived ROS may modulate the COX-2/PGE(2) axis in endothelial cells, which might play a relevant role in the pathophysiology of heart infarction.
  • Autores: Pérez Mozas, María (Autor de correspondencia); Payo Ollero, Jesús; Montiel Terrón, Veronica; et al.
    Revista: REVISTA ESPAÑOLA DE CIRUGIA ORTOPEDICA Y TRAUMATOLOGIA
    ISSN: 1888-4415 Vol.64 N° 5 2020 págs. 310-317
    Resumen
    BACKGROUND AND OBJECTIVE: Currently, there is no stablished pre-operative model that helps the orthopaedic surgeon predict the final graft diameter in anterior cruciate ligament reconstruction (ACLR). The purpose of this study was to determine whether there is a correlation between semitendinosus (ST) and gracilis (GT) cross-sectional area (CSA) evaluated pre-operatively in mm2 using magnetic resonance imaging (MRI) and the final intra-operative ST-GT autograft diameter in mm2.
  • Autores: Mariscal, G. (Autor de correspondencia); Nuñez, J. H.; Figueira, P.; et al.
    Revista: JOURNAL OF CRANIOVERTEBRAL JUNCTION AND SPINE
    ISSN: 0974-8237 Vol.11 N° 1 2020 págs. 31
  • Autores: Wu, M.; Claus, P. ; De Buck, S.; et al.
    Revista: EUROPEAN HEART JOURNAL
    ISSN: 0195-668X Vol.41 2020 págs. 1061 - 1061
  • Autores: Grigorian Shamagian, L.; Madonna, R.; Taylor, D.; et al.
    Revista: CIRCULATION RESEARCH
    ISSN: 0009-7330 Vol.124 N° 6 2019 págs. 938 - 951
    Resumen
    The myocardium consists of numerous cell types embedded in organized layers of ECM (extracellular matrix) and requires an intricate network of blood and lymphatic vessels and nerves to provide nutrients and electrical coupling to the cells. Although much of the focus has been on cardiomyocytes, these cells make up <40% of cells within a healthy adult heart. Therefore, repairing or regenerating cardiac tissue by merely reconstituting cardiomyocytes is a simplistic and ineffective approach. In fact, when an injury occurs, cardiac tissue organization is disrupted at the level of the cells, the tissue architecture, and the coordinated interaction among the cells. Thus, reconstitution of a functional tissue must reestablish electrical and mechanical communication between cardiomyocytes and restore their surrounding environment. It is also essential to restore distinctive myocardial features, such as vascular patency and pump function. In this article, we review the current status, challenges, and future priorities in cardiac regenerative or reparative medicine. In the first part, we provide an overview of our current understanding of heart repair and comment on the main contributors and mechanisms involved in innate regeneration. A brief section is dedicated to the novel concept of rejuvenation or regeneration, which we think may impact future development in the field. The last section describes regenerative therapies, where the most advanced and disruptive strategies used for myocardial repair are discussed. Our recommendations for priority areas in studies of cardiac regeneration or repair are summarized in Tables 1 and 2.
  • Autores: Martínez Turrillas, Rebeca; Rodríguez Díaz, Saray; Rodríguez Márquez, Paula; et al.
    Revista: STEM CELL RESEARCH
    ISSN: 1873-5061 Vol.41 2019 págs. 101626
    Resumen
    Primary Hyperoxaluria Type I (PH1) is a rare autosomal recessive metabolic disorder characterized by defects in enzymes involved in glyoxylate metabolism. PH1 is a life-threatening disease caused by the absence, deficiency or mistargeting of the hepatic alanine-glyoxylate aminotransferase (AGT) enzyme. A human induced pluripotent stem cell (iPSC) line was generated from dermal fibroblasts of a PH1 patient being compound heterozygous for the most common mutation c.508G>A (G170R), a mistargeting mutation, and c.364C>T (R122*), a previously reported nonsense mutation in AGTX. This iPSC line offers a useful resource to study the disease pathophysiology and a cell-based model for drug development.
  • Autores: Arellano-Viera, E.; Zabaleta, L.; Castano, J. ; et al.
    Revista: STEM CELL RESEARCH
    ISSN: 1873-5061 Vol.36 2019
    Resumen
    We have generated two human induced pluripotent stem cell (iPSC) lines from CD133(+) cells isolated from umbilical cord blood (CB) of a female child using non-integrative Sendai virus. Here we describe the complete characterization of these iPSC lines: PRYDi-CB5 and PRYDi-CB40.
  • Autores: Rosa, S.; Praca, C. ; Pitrez, P. R.; et al.
    Revista: SCIENTIFIC REPORTS
    ISSN: 2045-2322 Vol.9 2019 págs. 3826
    Resumen
    The current work reports the functional characterization of human induced pluripotent stem cells (iPSCs)-arterial and venous-like endothelial cells (ECs), derived in chemically defined conditions, either in monoculture or seeded in a scaffold with mechanical properties similar to blood vessels. iPSC-derived arterial- and venous-like endothelial cells were obtained in two steps: differentiation of iPSCs into endothelial precursor cells (CD31(pos)/KDRpos/VE-Cad(med)/EphB2(neg)/COUP-TFneg) followed by their differentiation into arterial and venous-like ECs using a high and low vascular endothelial growth factor (VEGF) concentration. Cells were characterized at gene, protein and functional levels. Functionally, both arterial and venous-like iPSC-derived ECs responded to vasoactive agonists such as thrombin and prostaglandin E2 (PGE(2)), similar to somatic ECs; however, arterial- like iPSC-derived ECs produced higher nitric oxide (NO) and elongation to shear stress than venous-like iPSC-derived ECs. Both cells adhered, proliferated and prevented platelet activation when seeded in poly(caprolactone) scaffolds. Interestingly, both iPSC-derived ECs cultured in monoculture or in a scaffold showed a different inflammatory profile than somatic ECs. Although both somatic and iPSC-derived ECs responded to tumor necrosis factor-alpha (TNF-alpha) by an increase in the expression of intercellular adhesion molecule 1 (ICAM-1), only somatic ECs showed an upregulation in the expression of E-selectin or vascular cell adhesion molecule 1 (VCAM-1).
  • Autores: Saludas Echauri, Laura; Garbayo Atienza, Elisa; Mazo Vega, Manuel María; et al.
    Revista: JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
    ISSN: 0022-3565 Vol.370 N° 3 2019 págs. 761 - 771
    Resumen
    Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are a promising cell source for cardiac repair after myocardial infarction (MI) because they offer several advantages such as potential to remuscularize infarcted tissue, integration in the host myocardium, and paracrine therapeutic effects. However, cell delivery issues have limited their potential application in clinical practice, showing poor survival and engraftment after transplantation. In this work, we hypothesized that the combination of hiPSC-CMs with microparticles (MPs) could enhance long-term cell survival and retention in the heart and consequently improve cardiac repair. CMs were obtained by differentiation of hiPSCs by small-molecule manipulation of the Wnt pathway and adhered to biomimetic poly(lactic-co-glycolic acid) MPs covered with collagen and poly(D-lysine). The potential of the system to support cell survival was analyzed in vitro, demonstrating a 1.70-fold and 1.99-fold increase in cell survival after 1 and 4 days, respectively. The efficacy of the system was tested in a mouse MI model. Interestingly, 2 months after administration, transplanted hiPSC-CMs could be detected in the peri-infarct area. These cells not only maintained the cardiac phenotype but also showed in vivo maturation and signs of electrical coupling. Importantly, cardiac function was significantly improved, which could be attributed to a paracrine effect of cells. These findings suggest that MPs represent an excellent platform for cell delivery in the field of cardiac repair, which could also be translated into an enhancement of the potential of cell-based therapies in other medical applications.
  • Autores: Grasa, J.; Pérez Ruiz, Ana Isabel; Munoz, M. J. ; et al.
    Revista: PROCEEDINGS OF THE INSTITUTION OF MECHANICAL ENGINEERS PART L-JOURNAL OF MATERIALS-DESIGN AND APPLICATIONS
    ISSN: 1464-4207 Vol.233 N° 8 2019 págs. 1594 - 1603
    Resumen
    Unlike other organs, skeletal muscle is endowed with a remarkable potential for regeneration that depends on the presence of satellite cells. Histological and functional (force generation) recoveries after muscle damage are not parallel processes. The aim of this study is to examine the in vivo contractile properties and in vitro passive stress-stretch behavior of muscle during degeneration-regeneration processes. Notexin was injected into rat tibialis anterior muscle, and functional recovery and histological changes were compared. We found that histological improvement of damaged muscle is delayed in comparison with its capacity to generate force. The elastic properties of muscle were not altered in agreement with the unchanged cross-linking index, probably as a consequence of the unaltered deposition of total collagen during degeneration-regeneration processes together with the maintenance of the ratio of collagens type I and III.
  • Autores: Pascual Gil de Gómez, Simón; Abizanda Sarasa, Gloria María; Iglesias López, Elena; et al.
    Revista: JOURNAL OF DRUG TARGETING
    ISSN: 1061-186X Vol.27 N° 43987 2019 págs. 573 - 581
    Resumen
    Neuregulin-1 loaded poly(lactic-co-glycolic acid) (PLGA) microparticles hold great promise for treating acute myocardial infarction, as they have been proved to recover heart function and induce positive heart remodelling in preclinical studies. More recently, the inflammatory response of the heart after acute myocardial infarction (AMI) has been identified as one of the major mechanisms in cardiac tissue remodelling and repair. However, the connection between neuregulin-1 PLGA microparticles and inflammation is still not well characterised. In the present study we assessed this relationship in a mouse AMI model. First, in vitro evidence indicated that neuregulin-1 PLGA microparticles induced a macrophage polarisation toward a regenerative phenotype (CD206+ cells), preventing macrophages from evolving toward the inflammatory phenotype (B7-2+ cells). This correlated with in vivo experiments, where neuregulin-1 PLGA microparticles locally improved the CD206+/B7-2+ ratio. Moreover, neuregulin-1 PLGA microparticles were administered at different time points (15¿min, 24, 72 and 168¿h) after infarction induction without causing secondary inflammatory issues. The time of treatment administration did not alter the inflammatory response. Taken together, these results suggest that neuregulin-1 PLGA microparticles can be administered depending on the therapeutic window of the encapsulated drug and that they enhance the heart's reparative inflammatory response after acute myocardial infarction, helping cardiac tissue repair.
  • Autores: Montiel Terrón, Veronica (Autor de correspondencia); Payo Ollero, Jesús; Amillo Garayoa, Santiago
    Revista: REVISTA ESPAÑOLA DE CIRUGIA ORTOPEDICA Y TRAUMATOLOGIA
    ISSN: 1888-4415 Vol.63 N° 4 2019 págs. 295 - 299
    Resumen
    Objetivo Conocer los resultados a largo plazo y el pronóstico de los pacientes que han sido intervenidos de resección de la primera fila del carpo (RPFC) en nuestro centro. Material y método Realizamos un estudio retrospectivo de 14 pacientes intervenidos de RPFC con un seguimiento de 3 a 16 años. Se evaluaron la movilidad, la capacidad funcional mediante el cuestionario Patient-Rated Wrist Evaluation (PRWE) y la capacidad para realizar las actividades de la vida diaria tras la intervención. Resultados El balance articular fue satisfactorio. La puntuación media en la escala PRWE fue de 20,9 ± 17,2 para la subescala de dolor y de 39 ± 35,5 para la subescala de funcionalidad. Ningún paciente había precisado reintervención ni han desarrollado complicaciones. El 80% de los pacientes estuvieron satisfechos o muy satisfechos. El 90% de los pacientes volvería a operarse. Discusión El rango de movimiento de la muñeca es similar con las diferentes técnicas de preservación de la movilidad. Los cambios artrósicos en la articulación radio-hueso grande secundarios a esta intervención no producen necesariamente dolor. Algunos autores han descrito que el grado de satisfacción de la RPFC es comparable con el de otros procedimientos, como la artrodesis en 4 esquinas con placa circular o artrodesis mediocarpiana con agujas. Conclusión La RPFC tiene alta tasa de satisfacción entre los pacientes con alivio del dolor, buena movilidad y funcionalidad postoperatoria de la muñeca. Además, presenta escasas complicaciones.
  • Autores: Raja, M. K.; Preobraschenski, J. ; Del Olmo-Cabrera, S.; et al.
    Revista: ELIFE
    ISSN: 2050-084X Vol.8 2019 págs. e40744
    Resumen
    Synaptophysins 1 and 2 and synaptogyrins 1 and 3 constitute a major family of synaptic vesicle membrane proteins. Unlike other widely expressed synaptic vesicle proteins such as vSNAREs and synaptotagmins, the primary function has not been resolved. Here, we report robust elevation in the probability of release of readily releasable vesicles with both high and low release probabilities at a variety of synapse types from knockout mice missing all four family members. Neither the number of readily releasable vesicles, nor the timing of recruitment to the readily releasable pool was affected. The results suggest that family members serve as negative regulators of neurotransmission, acting directly at the level of exocytosis to dampen connection strength selectively when presynaptic action potentials fire at low frequency. The widespread expression suggests that chemical synapses may play a frequency filtering role in biological computation that is more elemental than presently envisioned. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
  • Autores: Stuckensen, K.; Lamo de Espinosa Vázquez de Sola, José María; Muiños Lopez, Emma; et al.
    Revista: MATERIALS
    ISSN: 1996-1944 Vol.12 N° 19 2019 págs. 3105
    Resumen
    In the treatment of bone non-unions, an alternative to bone autografts is the use of bone morphogenetic proteins (BMPs), e.g., BMP-2, BMP-7, with powerful osteoinductive and osteogenic properties. In clinical settings, these osteogenic factors are applied using absorbable collagen sponges for local controlled delivery. Major side effects of this strategy are derived from the supraphysiological doses of BMPs needed, which may induce ectopic bone formation, chronic inflammation, and excessive bone resorption. In order to increase the efficiency of the delivered BMPs, we designed cryostructured collagen scaffolds functionalized with hydroxyapatite, mimicking the structure of cortical bone (aligned porosity, anisotropic) or trabecular bone (random distributed porosity, isotropic). We hypothesize that an anisotropic structure would enhance the osteoconductive properties of the scaffolds by increasing the regenerative performance of the provided rhBMP-2. In vitro, both scaffolds presented similar mechanical properties, rhBMP-2 retention and delivery capacity, as well as scaffold degradation time. In vivo, anisotropic scaffolds demonstrated better bone regeneration capabilities in a rat femoral critical-size defect model by increasing the defect bridging. In conclusion, anisotropic cryostructured collagen scaffolds improve bone regeneration by increasing the efficiency of rhBMP-2 mediated bone healing.
  • Autores: Pardo Saganta, Ana; Calvo, I. A.; Sáez Ochoa, Borja; et al.
    Revista: CURRENT STEM CELL REPORTS
    ISSN: 2198-7866 Vol.5 N° 1 2019 págs. 1 - 10
    Resumen
    Purpose of Review Stem cells reside in specialized anatomical locations called niches where supportive stromal cells and the extracellular matrix (ECM) regulate their self-renewal and differentiation. This review explores the critical roles of the ECM in stem cell maintenance in tissue homeostasis, aging, and disease. Recent Findings It is well established that ECM proteins and their biomechanical properties control stem cell fate. In addition to specific molecular interactions, the ECM composition determines the topology and stiffness of the substrate, which also regulate stem cell behavior. Changes in the ECM during aging and disease can impair cell-ECM interactions and ultimately contribute to aging and disease pathogenesis. Summary A deeper understanding of the mechanisms by which the ECM regulates stem cell behavior in health, as well as during aging and in disease states, will facilitate the development of therapeutic strategies. These therapies should focus on recovering normal matrix synthesis and deposition aiming at promoting endogenous repair.
  • Autores: Montiel Terrón, Veronica (Autor de correspondencia); Alfonso Olmos-García, Matías; Villas Tomé, Carlos; et al.
    Revista: FOOT AND ANKLE SURGERY
    ISSN: 1268-7731 Vol.25 N° 2 2019 págs. 158 - 164
    Resumen
    Background: Exostoses at the base of the distal phalanx of the great toe are usually asymptomatic. The literature has not generally considered them as the origin of a possible problem resulting from a pressure conflict between hallux and shoe (medial aspect) or second toe (lateral aspect) nor a potential complication of surgical correction of hallux valgus deformity. No studies, to our knowledge, have evaluated its possible correlation with other foot disorders. When one of these neglected exostoses became painful after surgical correction of hallux valgus, we decided to start a study to determine their possible origin, prevalence in daily practice and histo-pathological morphology. Methods: Two hundred and fifty-four feet of patients (average age 41.7. y.) were enrolled in the study from January 2007 to June 2009. Dorsoplantar weight-bearing radiographs were used to analyze the presence of exostoses and their correlation with the distal phalanx morphology, metatarsal formula (or transverse plane orientation of the metatarsal heads parabola) and hallux valgus angles. Patients were classified according to their age and main symptom for consultation. Four exostoses removed from cadaver feet were also analyzed microscopically. Results: Osseous excrescences arising on the medial or lateral aspect at the proximal part of the terminal phalanx of the hallux were observed in 132 feet (51.9%). Thirty-five feet out of these 132 (13.7%) had exostoses on both sides of the phalanx.A statistically significant positive correlation was found between the presence of a medial exostosis of the phalanx and the severity of HVA. Patients with higher IPH and asymmetry angles have a lower prevalence of medial exostoses (p. <. 0.05). Amongst the different morphologies of the second phalanx, exostoses were most likely found in the standard form. Conclusions: Prevalence of exostoses at the base of the distal phalanx is high (51.9% of the studied feet). Histological findings would suggest that these exostoses could be considered a mechanical reactive process, produced by a chronic irritation by shoes. We encourage surgeons to be aware of its potential clinical implications. Direct resection is very simple and the most appropriate treatment for symptomatic cases.
  • Autores: González Gil, Ana Belén; Lamo de Espinosa Vázquez de Sola, José María; Muiños Lopez, Emma; et al.
    Revista: JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
    ISSN: 1932-6254 Vol.13 N° 5 2019 págs. 742 - 752
    Resumen
    An attractive alternative to bone autografts is the use of autologous mesenchymal progenitor cells (MSCs) in combination with biomaterials. We compared the therapeutic potential of different sources of mesenchymal stem cells in combination with biomaterials in a bone nonunion model. A critical-size defect was created in Sprague-Dawley rats. Animals were divided into six groups, depending on the treatment to be applied: bone defect was left empty (CTL); treated with live bone allograft (LBA); hrBMP-2 in collagen scaffold (CSBMP2); acellular polycaprolactone scaffold (PCL group); PCL scaffold containing periosteum-derived MSCs (PCLPMSCs) and PCL containing bone marrow-derived MSCs (PCLBMSCs). To facilitate cell tracking, both MSCs and bone graft were isolated from green fluorescent protein (GFP)-transgenic rats. CTL group did not show any signs of healing during the radiological follow-up (n = 6). In the LBA group, all the animals showed bone bridging (n = 6) whereas in the CSBMP2 group, four out of six animals demonstrated healing. In PCL and PCLPMSCs groups, a reduced number of animals showed radiological healing, whereas no healing was detected in the PCLBMSCs group. Using microcomputed tomography, the bone volume filling the defect was quantified, showing significant new bone formation in the LBA, CSBMP2, and PCLPMSCs groups when compared with the CTL group. At 10 weeks, GFP positive cells were detected only in the LBA group and restricted to the outer cortical bone in close contact with the periosteum. Tracking of cellular implants demonstrated significant survival of the PMSCs when compared with BMSCs. In conclusion, PMSCs improve bone regeneration being suitable for mimetic autograft design.
  • Autores: Riera Alvarez, Luis; Pons de Villanueva, Juan (Autor de correspondencia)
    Revista: JOURNAL OF PEDIATRIC ORTHOPAEDICS-PART B
    ISSN: 1060-152X Vol.28 N° 6 2019 págs. 553 - 554
    Resumen
    Buckle or torus fractures in the distal forearm are characterized by a bulging of the cortical bone. They are a frequent reason for consultation in pediatric emergencies. The treatment and follow-up of this type of fractures varies from soft immobilizations to a plaster cast. The purpose of this study is to assess the stability of buckle fractures of the distal radius. We reviewed 106 pediatric patients with buckle fractures and analyzed the radiographs at the time of initial consultation and at the last follow-up. None of these fractures displaced further, regardless of the treatment given. Buckle or torus fractures do not need follow-up radiographs. As they are stable, the simpler immobilization treatment is sufficient.
  • Autores: Sanchez-Moreno, I. (Autor de correspondencia); Benito-Arenas, R.; Montero Calle, Maria del Pilar; et al.
    Revista: ACS OMEGA
    ISSN: 2470-1343 Vol.4 N° 6 2019 págs. 10593 - 10598
    Resumen
    An efficient multienzyme system for the preparatiy e synthesis of D-xylonate, a chemical with versatile industrial applications, is described. The multienzyme system is based on D-xylose oxidation catalyzed by the xylose dehydrogenase from Calulobacter crescentus and the use of catalytic amounts of NAD(+). The cofactor is regenerated in situ by coupling the reduction of acetaldehyde into ethanol catalyzed by alcohol dehydrogenase from Clostridium kluyveri. Excellent conversions (>95%) were obtained in a process that allows easy product isolation by simple evaporation of the volatile buffer and byproducts.
  • Autores: Valentí Azcárate, Andrés; Montiel Terrón, Veronica; Alfonso Olmos-García, Matías; et al.
    Revista: THE FOOT
    ISSN: 0958-2592 Vol.38 2019 págs. 39 - 42
    Resumen
    Background: Having had a previous experience of 4 open F2 osteotomies to correct interphalangeal hallux valgus, the aim of this study was to test the efficacy of a percutaneous approach for this correction. Methods: 3 open and 12 percutaneous F2 osteotomies in 15 cadaver feet were performed. Interphalangeal (IPH), F2 asymmetry (AF2) and joint deviation (JD) angles were measured on radiographs. The operated great toes were anatomically analyzed looking for possible lesions to surrounding tissues. Results: Mean IPH decreased from 10.7° to 2.9°, AF2 from 7.8° to 1°, and JD from 1.4° to 0.5°. Damage to the hallux extensor tendon was detected in 1 foot and a nail bed lesion was detected in 1 case, both operated percutaneously. Conclusions: F2 Valgus deformity can be corrected using open or percutaneous osteotomy. The authors consider the open correction worthwhile because percutaneous techniques may damage surrounding tissues and the incision length difference is minor. Level of clinical evidence: 3.
  • Autores: Pardo Saganta, Ana; Vera Álvarez, Laura; Petri González, Eva; et al.
    Revista: EUROPEAN RESPIRATORY JOURNAL
    ISSN: 0903-1936 Vol.54 N° Supl. 63 2019
  • Autores: Martin Mallo, Angel; Martínez Turrillas, Rebeca; Rodriguez, S.; et al.
    Revista: HUMAN GENE THERAPY
    ISSN: 1043-0342 Vol.30 N° 11 2019 págs. A182 - A182
  • Autores: Sáenz de Pipaon Echarren, Goren; David, L.; Maillo, A.; et al.
    Revista: ATHEROSCLEROSIS
    ISSN: 0021-9150 Vol.287 2019 págs. E65 - E65
  • Autores: Trujillo, D. C.; Santamaria, E. M.; Larequi Ardanáz, Eduardo; et al.
    Revista: HEPATOLOGY
    ISSN: 0270-9139 Vol.70 2019 págs. 1101A - 1102A
  • Autores: Pérez Estenaga, Íñigo; Prosper Cardoso, Felipe; Pelacho Samper, Beatriz (Autor de correspondencia)
    Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
    ISSN: 1422-0067 Vol.19 N° 10 2018 págs. E3236
    Resumen
    Coronary heart disease is the leading cause of death worldwide with huge socio-economic consequences. Cell therapy, and particularly mesenchymal stem cells (MSC), are considered a promising option to treat this disorder, due to their robust trophic and immunomodulatory properties. However, limitations such as their low rate of engraftment and poor survival after administration into the heart have precluded their large-scale clinical use. Nevertheless, the combination of MSC with polymer-made scaffolds or hydrogels has proven to enhance their retention and, therefore, their efficacy. Additionally, their allogeneic use could permit the creation of ready-to-use cell patches able to improve their feasibility and promote their application in clinical settings. In this review, the experimental and clinical results derived from the use of MSC in cardiac pathology, as well as advances in the bioengineering field to improve the potential of therapeutic cells, are extensively discussed. Additionally, the current understanding of the heart response to the allogeneic MSC transplants is addressed.
  • Autores: Macri-Pellizzeri, Laura; Juan Pardo, María Elena; Prosper Cardoso, Felipe; et al.
    Revista: JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
    ISSN: 1932-6254 Vol.12 N° 4 2018 págs. 1012 - 1019
    Resumen
    Tissue-specific stem cells reside in a specialized environment known as niche. The niche plays a central role in the regulation of cell behaviour and, through the concerted action of soluble molecules, supportive somatic cells, and extracellular matrix components, directs stem cells to proliferate, differentiate, or remain quiescent. Great efforts have been done to decompose and separately analyse the contribution of these cues in the in vivo environment. Specifically, the mechanical properties of the extracellular matrix influence many aspects of cell behaviour, including self-renewal and differentiation. Deciphering the role of biomechanics could thereby provide important insights to control the stem cells responses in a more effective way with the aim to promote their therapeutic potential. In this review, we provide a wide overview of the effect that the microenvironment stiffness exerts on the control of cell behaviour with a particular focus on the induction of stem cells differentiation. We also describe the process of mechanotransduction and the molecular effectors involved. Finally, we critically discuss the potential involvement of tissue biomechanics in the design of novel tissue engineering strategies
  • Autores: Lamo de Espinosa Vázquez de Sola, José María; Mora Gasque, Gonzalo; Blanco, J. F.; et al.
    Revista: JOURNAL OF TRANSLATIONAL MEDICINE
    ISSN: 1479-5876 Vol.16 2018 págs. 213
    Resumen
    Background: Mesenchymal stromal cells (MSCs) are a promising option to treat knee osteoarthritis (OA). Their safety and usefulness have been reported in several short-term clinical trials but less information is available on the long-term effects of MSC in patients with osteoarthritis. We have evaluated patients included in our previous randomized clinical trial (CMM-ART, NCT02123368) to determine their long-term clinical effect. Materials: A phase I/II multicenter randomized clinical trial with active control was conducted between 2012 and 2014. Thirty patients diagnosed with knee OA were randomly assigned to Control group, intraarticularly administered hyaluronic acid alone, or to two treatment groups, hyaluronic acid together with 10 x 10(6) or 100 x 10(6) cultured autologous bone marrow-derived MSCs (BM-MSCs), and followed up for 12 months. After a follow up of 4 years adverse effects and clinical evolution, assessed using VAS and WOMAC scorings are reported. Results: No adverse effects were reported after BM-MSCs administration or during the follow-up. BM-MSCs-administered patients improved according to VAS, median value (IQR) for Control, Low-dose and High-dose groups changed from 5 (3, 7), 7 (5, 8) and 6 (4, 8) to 7 (6, 7), 2 (2, 5) and 3 (3, 4), respectively at the end of follow up (Low-dose vs Control group, p = 0.01; High-dose vs Control group, p = 0.004). Patients receiving BM-MSCs also improved clinically according to WOMAC. Control group showed an increase median value of 4 points (-11;10) while Low-dose and High-dose groups exhibited values of -18 (-28;-9) and -10 (-21;-3) points, respectively (Low-dose vs Control group p = 0.043). No clinical differences between the BM-MSCs receiving groups were found. Conclusions: Single intraarticular injection of in vitro expanded autologous BM-MSCs is a safe and feasible procedure that results in long-term clinical and functional improvement of knee OA.
  • Autores: Linares Acosta, Javier; Lopez-Muneta, L.; Arellano-Viera, E.; et al.
    Revista: STEM CELL RESEARCH
    ISSN: 1873-5061 Vol.33 2018 págs. 125 - 129
    Resumen
    Islet-1 (Isl1) is a transcription factor essential for life expressed in specific cells with different developmental origins. We have generated iPSC lines from fibroblasts of the transgenic Ai6 x Isl1-Cre (Ai6IslCre) mouse. Here we describe the complete characterization of four iPSC lines: ATCi-Ai6IslCre10, ATCi-Ai6IslCre35, ATCi-Ai6IslCre74 and ATCi-Ai6IslCre80.
  • Autores: Rodríguez García, José Antonio; Orbe Lopategui, Josune; Saenz-Pipaon, G.; et al.
    Revista: THROMBOSIS RESEARCH
    ISSN: 0049-3848 Vol.170 2018 págs. 1 - 9
    Resumen
    Introduction: Wound healing after myocardial infarction (MI) is mediated by different cell types, secreted proteins, components of the extracellular matrix (ECM) and, as increasing evidences suggest, extracellular vesicles (EVs). We aim to determine the dynamics of release and origin of EVs after MI, as well as their biological activity on endothelial cells (ECs). Methods: MI was induced in WT mice and blood and tissues collected at baseline, 3, 15 and 30 days post-ligation for cardiac function (echocardiography) and histological evaluation. Circulating EVs subpopulations were measured by flow cytometry in mouse, and in a small cohort of patients with ST-segment elevation MI (STEMI, n= 6). In vitro, EVs were isolated from a cardiomyocyte cell line (HL1) and their function assayed on ECs. Results: Leukocyte and endothelial EVs increased concomitant to inflammatory and angiogenic processes triggered by ischemia. More strikingly, cardiomyocyte EVs (connexin43+) were detected in STEMI patients and in murine MI, where a significant increase in their levels was reported at day 15 post-ischemia (p < 0.05 vs baseline). In vitro, HL1EVs induced ECs migration (p= 0.05) and proliferation (p < 0.05), but impaired tube formation. These apparent contradictory results could be partially explained by the upregulation of MMP3, and the apoptosis and senescence genes, p53 and p16, induced by HL1EVs on ECs (p < 0.05). Conclusions: MI induces the release of different EVs subpopulations, including those of cardiac origin, in a preclinical model of MI and STEMI patients. In vitro, cardiomyocyte derived EVs are able to modulate endothelial function, suggesting their active role in heart repair after ischemia.
  • Autores: Garate, A.; Sanchez, P.; Delgado, D.; et al.
    Revista: JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
    ISSN: 1549-3296 Vol.106 N° 2 2018 págs. 377 - 385
    Resumen
    In the field of tissue engineering, diverse types of bioscaffolds are being developed currently for osteochondral defect applications. In this work, a novel scaffold based on platelet rich plasma (PRP) and hyaluronic acid with mesenchymal stem cells (MSCs) has been evaluated to observe its effect on immobilized cells. The bioscaffolds were prepared by mixing different volumes of synovial fluid (SF) with PRP from patients obtaining three formulations at PRP-SF ratios of 3:1, 1:1 and 1:3 (v/v). The live/dead staining revealed that although the cell number of each type of bioscaffold was different, these this constructs provide cells with a suitable environment for their viability and proliferation. Moreover, immobilized MSCs showed their ability to secrete fibrinolytic enzymes, which vary depending on the fibrin amount of the scaffold. Immunohistochemical analysis revealed the positive staining for collagen type II in all cases, proving the biologic action of SF derived MSCs together with the suitable characteristics of the bioscaffold for chondrogenic differentiation. Considering all these aspects, this study demonstrates that these cells-based constructs represent an attractive method for cell immobilization, achieving completely autologous and biocompatible scaffolds. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 377-385, 2018.
  • Autores: Castellano, D.; Sanchis, A.; Blanes, M.; et al.
    Revista: JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
    ISSN: 1932-6254 Vol.12 N° 2 2018 págs. E983 - E994
    Resumen
    Human dermo-epidermal skin equivalents (DE) comprising in vitro expanded autologous keratinocytes and fibroblasts are a good option for massive burn treatment. However, the lengthy expansion time required to obtain sufficient surface to cover an extensive burn together with the challenging surgical procedure limits their clinical use. The integration of DE and biodegradable scaffolds has been proposed in an effort to enhance their mechanical properties. Here, it is shown that poly(hydroxybutyrate) electrospun scaffolds (PHB) present good biocompatibility both in vitro and in vivo and are superior to poly-epsilon-caprolactone electrospun scaffolds as a substrate for skin reconstruction. Implantation of PHB scaffolds in healthy rats polarized macrophages to an M2-type that promoted constructive in vivo remodelling. Moreover, implantation of DE-PHB composites in a NOD/SCID mouse xenograft model resulted in engraftment accompanied by an increase in angiogenesis that favoured the survival of the human graft. Thus, PHB scaffolds are an attractive substrate for further exploration in skin reconstruction procedures, probably due in part to their greater angiogenic and M2 macrophage polarization properties. Copyright (c) 2017 John Wiley & Sons, Ltd.
  • Autores: Stuckensen, K.; Schwab, A.; Knauer, M.; et al.
    Revista: ADVANCED MATERIALS
    ISSN: 0935-9648 Vol.30 N° 28 2018 págs. e1706754
    Resumen
    An integral approach toward in situ tissue engineering through scaffolds that mimic tissue with regard to both tissue architecture and biochemical composition is presented. Monolithic osteochondral and meniscus scaffolds are prepared with tissue analog layered biochemical composition and perpendicularly oriented continuous micropores by a newly developed cryostructuring technology. These scaffolds enable rapid cell ingrowth and induce zonal-specific matrix synthesis of human multipotent mesenchymal stromal cells solely through their design without the need for supplementation of soluble factors such as growth factors.
  • Autores: Montiel Terrón, Veronica; Muiños Lopez, Emma; Granero Molto, Froilan; et al.
    Revista: M.L.T.J. MUSCLES, LIGAMENTS AND TENDONS JOURNAL
    ISSN: 2240-4554 Vol.8 N° 2 2018 págs. 261-275
    Resumen
    Conclusion: Animal models for muscular degeneration after rotator cuff tears have been well established and described. The next challenge is the achievement of a therapeutic target that could be transferred to the clinical setting.
  • Autores: Albiñana Cunninghan, Juan Newton; Ripalda Cemborain, Purificación; Labiano Miravalles, Tania; et al.
    Revista: JOURNAL OF ORTHOPAEDIC SURGERY AND RESEARCH
    ISSN: 1749-799X Vol.13 2018 págs. 72
    Resumen
    Background: TGF-beta has been described as a mediator of fibrosis and scarring. Several studies achieved reduction in experimental scarring through the inhibition of TGF-beta. Fibroblasts have been defined as the cell population originating fibrosis, blocking fibroblast invasion may impair epidural fibrosis appearance. For this purpose, biocompatible materials used as mechanical barriers and a TGF-beta inhibitor peptide were evaluated in the reduction of epidural fibrosis. Methods: A L6 laminectomy was performed in 40 New Zealand white rabbits. Divided into four groups, each rabbit was assigned to receive either collagen sponge scaffold (CS group), gelatin-based gel (GCP group), P144 (R) (iTGF beta group), or left untreated (control group). Four weeks after surgery, cell density, collagen content, and new bone formation of the scar area were determined by histomorphometry. Two experienced pathologists scored dura mater adhesion, scar density, and inflammatory infiltrate in a blinded manner. Results: In all groups, laminectomy site was filled with fibrous tissue and the dura mater presented adhesions. Only GCP group presented a significant reduction in collagen content and scar density. Conclusion: GCP treatment reduces epidural fibrosis although did not prevent dura mater adhesion completely.
  • Autores: Apaolaza Emparanza, Iñigo; San José Enériz, Edurne; Aguirre Ena, Xabier; et al.
    Revista: MOLECULAR AND CELLULAR ONCOLOGY
    ISSN: 2372-3556 Vol.30 N° 5 2018 págs. e1389672.
    Resumen
    The identification of therapeutic strategies exploiting the metabolic alterations of malignant cells is a relevant area in cancer research. Here, we discuss a novel computational method, based on the COBRA (COnstraint-Based Reconstruction and Analysis) framework for metabolic networks, to perform this task. Current and future steps are presented.
  • Autores: Valentí Azcárate, Andrés; Payo Ollero, Jesús (Autor de correspondencia); Pérez Mozas, María; et al.
    Revista: KNEE
    ISSN: 0968-0160 Vol.25 N° 5 2018 págs. 790 - 798
    Resumen
    Background: There are no well-established guidelines for safe driving after injury or surgical treatment. The purpose of this study was to assess the aptitude to regain driving skills and brake reaction abilities after anterior cruciate ligament (ACL) surgery. Methods: This study compared the driving abilities and skills at four to six weeks after surgery of 31 patients who underwent ACL reconstruction with hamstring autograft with 31 healthy volunteers. Multiple variables, including pedestrian impact, car crash, red traffic light violations, visual reaction time, and other driving abilities were measured with a validated driving simulator. Results: There was no statistically significant between-group difference with respect to skill, driving ability, and brake reaction times (P > 0.05). The differences between right and left knees were also not statistically significant (P > 0.05). However, patients with a right ACL reconstruction had a higher number of collisions with fixed objects (2.82 vs. 1.84, P = 0.239) and pedestrian impacts (0.23 vs. 0.00 P = 0.221), and had slower brake reaction times (585.69 vs. 456.02 ms, P = 0.069). The Tegner score was similar in each group (7.19 in ACL reconstruction group vs. 6.8 in control group, P = 0.092) and the Lysholm score improved as compared with the presurgical measurement (53.48 vs. 89.61, P < 0.001). Conclusions: Anterior cruciate ligament surgery with hamstring autograft did not result in a decrease in driving performance and safety at four to six weeks after surgery with respect to skill, ability to drive, and brake response time. (C) 2018 Elsevier B.V. All rights reserved.
  • Autores: Beerens, M.; Aranguren López, Xabier; Hendrickx, B. ; et al.
    Revista: SCIENTIFIC REPORTS
    ISSN: 2045-2322 Vol.8 2018
    Resumen
    Lymphatic capillary growth is an integral part of wound healing, yet, the combined effectiveness of stem/progenitor cells on lymphatic and blood vascular regeneration in wounds needs further exploration. Stem/progenitor cell transplantation also emerged as an approach to cure lymphedema, a condition caused by lymphatic system deficiency. While lymphedema treatment requires lymphatic system restoration from the capillary to the collector level, it remains undetermined whether stem/progenitor cells support a complex regenerative response across the entire anatomical spectrum of the system. Here, we demonstrate that, although multipotent adult progenitor cells (MAPCs) showed potential to differentiate down the lymphatic endothelial lineage, they mainly trophically supported lymphatic endothelial cell behaviour in vitro. In vivo, MAPC transplantation supported blood vessel and lymphatic capillary growth in wounds and restored lymph drainage across skin flaps by stimulating capillary and pre-collector vessel regeneration. Finally, human MAPCs mediated survival and functional reconnection of transplanted lymph nodes to the host lymphatic network by improving their (lymph) vascular supply and restoring collector vessels. Thus, MAPC transplantation represents a promising remedy for lymphatic system restoration at different anatomical levels and hence an appealing treatment for lymphedema. Furthermore, its combined efficacy on lymphatic and blood vascular growth is an important asset for wound healing.
  • Autores: Montes-Medina, L. ; Hernandez-Fernandez, A.; Gutierrez-Rivera, A. ; et al.
    Revista: INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED
    ISSN: 0020-1383 Vol.49 N° 11 2018 págs. 1979 - 1986
    Resumen
    Acceleration of the consolidation of the distracted bone is a relevant medical need. As a platform to improve in vivo bone engineering, we developed a novel distraction osteogenesis (DO) model in a rabbit large bone (femur) and tested if the application of cultured bone marrow stromal cells (BMSCs) immediately after the osteotomy promotes the formation of bone. This report consists of two components, an animal study to evaluate the quality of the regenerate following different treatments and an in vitro study to evaluate osteogenic potential of BMSC cultures. To illuminate the mechanism of action of injected cells, we tested stem cell cultures enriched in osteogenic-BMSCs (O-BMSCs) as compared with cultures enriched in non-osteogenic BMSCs (NO-BMSCs). Finally, we included a group of animals treated with biomaterials (fibrin and ground cortical bone) in addition to cells. Injection of O-BMSCs promoted the maturity of distracted callus and decreased fibrosis. When combined with biomaterials, O-BMSCs modified the ossification pattern from endochondral to intramembranous type. The use of NO-BMSCs not only did not increase the maturity but also increased porosity of the bone. These preclinical results indicate that the BMSC cultures must be tested in vitro prior to clinical use, since a number of factors may influence their outcome in bone formation. We hypothesize that the use of osteogenic BMSCs and biomaterials could be clinically beneficial to shorten the consolidation period of the distraction and the total period of bone lengthening. (C) 2018 Elsevier Ltd. All rights reserved.
  • Autores: Zabaleta Lasarte, Nerea; Barberia, M.; Martin-Higueras, C. ; et al.
    Revista: MOLECULAR THERAPY
    ISSN: 1525-0016 Vol.26 N° 5 2018 págs. 384 - 385
  • Autores: Zabaleta Lasarte, Nerea; Torella, L. ; Rodríguez Díaz, Saray; et al.
    Revista: HUMAN GENE THERAPY
    ISSN: 1043-0342 Vol.29 N° 12 2018 págs. A108 - A108
  • Autores: Knipe, R. S.; Spinney, J. J.; Franklin, A.; et al.
    Revista: AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
    ISSN: 1073-449X Vol.197 2018
  • Autores: Pelacho Samper, Beatriz; López Díaz de Cerio, Ascensión; Inoges Sancho, Susana Inmaculada; et al.
    Revista: EUROPEAN HEART JOURNAL
    ISSN: 0195-668X Vol.39 N° Supl. 1 2018 págs. 1196 - 1196

Proyectos desde 2018

  • Título: Dissecting the Role of the Immune Microenvironment in Myelodysplastic Syndromes.
    Código de expediente: 0011-3947-2022-000004
    Investigador principal: IRENE GAÑAN GOMEZ.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2023 GN Andia - Atracción de talento
    Fecha de inicio: 30-12-2023
    Fecha fin: 29-12-2028
    Importe concedido: 525.000,00€
    Otros fondos: -
  • Título: GN 2023 INVESTIGO Antonio Porlan (F.P.)
    Código de expediente: 0011-4001-2023-000086
    Investigador principal:
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: FIMA 2023 GN Investigo
    Fecha de inicio: 20-11-2023
    Fecha fin: 19-11-2024
    Importe concedido: 33.003,92€
    Otros fondos: -
  • Título: GNI 2022 INVESTIGO Anaut Lusar Ilazki 2 MANU MAZO
    Código de expediente: 0011-4001-2023-000081
    Investigador principal: ILAZKI ANAUT LUSAR, ILAZKI ANAUT LUSAR.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: FIMA 2021 GN Investigo
    Fecha de inicio: 19-10-2023
    Fecha fin: 18-10-2024
    Importe concedido: 33.003,92€
    Otros fondos: Fondos MRR
  • Título: Desarrollo de miocardio ingenierizado maduro por estimulación electromecánica y análisis no invasivo del proceso
    Código de expediente: 0011-1408-2023-000014
    Investigador principal: MARIA ALEJANDRA RODRIGUEZ PARDO, MARIA ALEJANDRA RODRIGUEZ PARDO.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: FIMA 2023 -GN DOCTORANDOS INDUSTRIALES 2023-2025
    Fecha de inicio: 29-09-2023
    Fecha fin: 28-09-2026
    Importe concedido: 73.933,04€
    Otros fondos: -
  • Título: Investigating thransthyretin amyloid cardiomyopathy through advanced disease modeling
    Código de expediente: PID2022-142807OA-I00
    Investigador principal: OLALLA Iglesias GARCIA.
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: FIMA 2022 MCIU AEI GENERACION CONOCIMIENTO
    Fecha de inicio: 01-09-2023
    Fecha fin: 31-08-2026
    Importe concedido: 162.500,00€
    Otros fondos: Fondos MRR
  • Título: Desarrollo de Medicamentos Innovadores basados en CAR-T: Datos, Inteligencia Artificial, secuenciación MAsiva y Nano-Tecnología (DIAMANTE)
    Código de expediente: 0011-1411-2023-000074
    Investigador principal: JUAN ROBERTO RODRIGUEZ MADOZ.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: FIMA 2023 GN PROYECTOS ESTRATEGICOS DE I+D 2023-2026
    Fecha de inicio: 01-07-2023
    Fecha fin: 31-12-2025
    Importe concedido: 422.584,33€
    Otros fondos: -
  • Título: Desarrollo de Medicamentos Innovadores basados en CAR-T: Datos, Inteligencia Artificial, secuenciación MAsiva y Nano-Tecnología (DIAMANTE). Proyecto financiado en el marco de la convocatoria 2023 de proyectos Estratégicos de Gobierno de Navarra
    Código de expediente: 0011-1411-2023-000105
    Investigador principal: FELIPE LUIS PROSPER CARDOSO.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2023 GN PROYECTOS ESTRATEGICOS DE I+D 2023-2026
    Fecha de inicio: 01-07-2023
    Fecha fin: 31-12-2025
    Importe concedido: 362.076,16€
    Otros fondos: -
  • Título: Plataforma para la Identificación de TCR Específicos de Antígenos Tumorales para la Inmunoterapia de Tumores Sólidos (PITAGORAS)
    Código de expediente: 0011-1411-2023-000107
    Investigador principal: ASCENSION LOPEZ DIAZ DE CERIO.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2023 GN PROYECTOS ESTRATEGICOS DE I+D 2023-2026
    Fecha de inicio: 01-07-2023
    Fecha fin: 31-12-2025
    Importe concedido: 474.228,40€
    Otros fondos: -
  • Título: RYC2021¿032197¿I NURIA PLANELL
    Código de expediente: RYC2021-032197-I
    Investigador principal: FELIPE LUIS PROSPER CARDOSO, NURIA PLANELL PICOLA.
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: FIMA 2021 MCIU RAMÓN Y CAJAL
    Fecha de inicio: 01-01-2023
    Fecha fin: 31-12-2027
    Importe concedido: 236.350,00€
    Otros fondos: Fondos FSE
  • Título: Estrategias de tratamiento temprano de la osteomielitis en la prevención de la pseudoartrosis de fractura
    Código de expediente: GN2022/06
    Investigador principal: FROILAN GRANERO MOLTO.
    Financiador: GOBIERNO DE NAVARRA. DEPARTAMENTO DE SALUD
    Convocatoria: 2022 GN Proyectos de Investigación en salud
    Fecha de inicio: 22-12-2022
    Fecha fin: 21-12-2024
    Importe concedido: 48.875,00€
    Otros fondos: -
  • Título: PTA2021- P. AGUIRRE F. Prosper
    Código de expediente: PTA2021-020262-I
    Investigador principal: FELIPE LUIS PROSPER CARDOSO.
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: FIMA 2021 MINECO TÉCNICOS DE APOYO
    Fecha de inicio: 01-11-2022
    Fecha fin: 31-10-2025
    Importe concedido: 42.600,00€
    Otros fondos: -
  • Título: Fabricación, celularización, caracterización y análisis de tejidos cardiacos humanos ingenierizados 3D
    Código de expediente: 0011-4001-2022-000027
    Investigador principal: MANUEL MARIA MAZO VEGA, ILAZKI ANAUT LUSAR.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: FIMA 2021 GN Investigo
    Fecha de inicio: 19-10-2022
    Fecha fin: 18-10-2023
    Importe concedido: 33.108,92€
    Otros fondos: -
  • Título: Biotecnología aplicada a la generación de órganos a partir de células madres
    Código de expediente: PID2021-122589OB-I00
    Investigador principal: XABIER ARANGUREN LOPEZ.
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: FIMA 2021 MCIU AEI GENERACION CONOCIMIENTO
    Fecha de inicio: 01-09-2022
    Fecha fin: 31-08-2025
    Importe concedido: 145.200,00€
    Otros fondos: -
  • Título: SOCRATHeS: DeSarrollO de terapias CAR-T innovadoras para el trAtamiento de Tumores Hematológicos y Sólidos
    Código de expediente: 0011-1411-2022-000088
    Investigador principal: JUAN JOSE LASARTE SAGASTIBELZA.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: FIMA 2022 GN PROYECTOS ESTRATEGICOS DE I+D 2022-2025
    Fecha de inicio: 01-05-2022
    Fecha fin: 30-12-2024
    Importe concedido: 540.969,38€
    Otros fondos: -
  • Título: DeSarrollO de terapias CAR-T innovadoras para el trAtamiento de Tumores Hematológicos y Sólidos (SOCRATHeS)
    Código de expediente: 0011-1411-2022-000053
    Investigador principal: FELIPE LUIS PROSPER CARDOSO, FELIPE LUIS PROSPER CARDOSO.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2022 GN PROYECTOS ESTRATEGICOS DE I+D 2022-2025
    Fecha de inicio: 01-05-2022
    Fecha fin: 30-12-2024
    Importe concedido: 371.489,00€
    Otros fondos: -
  • Título: BIOHEART: Bioingeniería avanzada para el desarrollo del tejido cardiaco y su aplicación al estudio y detección de cardiotoxicidad
    Código de expediente: 0011-1411-2022-000092
    Investigador principal: XABIER ARANGUREN LOPEZ.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: FIMA 2022 GN PROYECTOS ESTRATEGICOS DE I+D 2022-2025
    Fecha de inicio: 01-04-2022
    Fecha fin: 31-12-2024
    Importe concedido: 518.435,82€
    Otros fondos: -
  • Título: Terapias avanzadas
    Código de expediente: RD21/0017/0009
    Investigador principal: FELIPE LUIS PROSPER CARDOSO.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2021 AES Redes de Investigación cooperativa orientadas a resultados (RICORS)
    Fecha de inicio: 01-01-2022
    Fecha fin: 31-12-2024
    Importe concedido: 94.947,60€
    Otros fondos: Fondos FEDER
  • Título: MEDICINA DE PRECISIÓN GENÓMICA EN NEOPLASIAS
    Código de expediente: PMP21/00015
    Investigador principal: FELIPE LUIS PROSPER CARDOSO.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2021 AES Medicina Personalizada
    Fecha de inicio: 01-01-2022
    Fecha fin: 31-12-2025
    Importe concedido: 213.000,00€
    Otros fondos: Fondos MRR
  • Título: MYCOMBIO. USO DE LA INHIBICIÓN DE MYC PARA SUPERAR LA RESISTENCIA A LA INMUNOTERAPIA EN NSCLC IMPULSADO POR KRAS CON DIVERSOS PERFILES MUTACIONALES
    Código de expediente: PLEC2021-007959
    Investigador principal: SILVESTRE VICENT CAMBRA.
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: FIMA 2021 MCI - AEI PROYECTOS DE I+D+I EN LINEAS ESTRATEGICAS FIMA 2021 MCI - AEI PROYECTOS DE I+D+I EN LINEAS ESTRATEGICAS
    Fecha de inicio: 01-12-2021
    Fecha fin: 30-11-2024
    Importe concedido: 277.624,13€
    Otros fondos: Fondos MRR
  • Título: New targets and designs to improve CAR-T cell based immunotherapy against pancreatic cancer (CarPanTu)
    Código de expediente: PLEC2021-008094
    Investigador principal: FELIPE LUIS PROSPER CARDOSO.
    Financiador: AGENCIA ESTATAL DE INVESTIGACION
    Convocatoria: 2021 AEI Proyectos de I+D+i en líneas estratégicas
    Fecha de inicio: 01-11-2021
    Fecha fin: 31-10-2024
    Importe concedido: 100.042,00€
    Otros fondos: Fondos MRR
  • Título: Targeting the tumor microenvironment to improve CAR-T cell based immunotherapy in pancreatic canceronment to improve CAR-T cell b
    Código de expediente: PLEC2021-008094
    Investigador principal: JUAN JOSE LASARTE SAGASTIBELZA.
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: FIMA 2021 MCI - AEI PROYECTOS DE I+D+I EN LINEAS ESTRATEGICAS
    Fecha de inicio: 01-10-2021
    Fecha fin: 30-09-2024
    Importe concedido: 104.207,00€
    Otros fondos: -
  • Título: Desarrollo de nanopartículas de CRISPR para el tratamiento del remodelado adverso en la cardiomiopatía isquémica
    Código de expediente: 0011-1408-2021-000013
    Investigador principal: NEREA GARITANO LARREA.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: FIMA 2021 -GN DOCTORANDOS INDUSTRIALES 2021- 2023
    Fecha de inicio: 01-09-2021
    Fecha fin: 31-08-2024
    Importe concedido: 86.168,40€
    Otros fondos: -
  • Título: GNE 2020 PREDOC AINTZANE DIAZ F. PROSPER
    Código de expediente: 0011-0537-2020-000022
    Investigador principal: AINTZANE DIAZ MAZQUIARAN.
    Financiador: GOBIERNO DE NAVARRA / DPTO. EDUCACIÓN CULTURA Y TURISMO
    Convocatoria: FIMA GNE 2020 BECAS PREDOCTORALES FIMA GNE 2020 BECAS PREDOCTORALES
    Fecha de inicio: 10-06-2021
    Fecha fin: 14-10-2023
    Importe concedido: 57.802,05€
    Otros fondos: -
  • Título: Estudio genómico para la personalización del diagnóstico y el tratamiento de los pacientes con insuficiencia Cardíaca crónica y enfermedad renal crónica (Medicina cardIoreNal pERsonalizada en NaVArra)-II (MINERVA-II)
    Código de expediente: 0011-1411-2021-000068
    Investigador principal: ARANZAZU GONZALEZ MIQUEO, ARANZAZU GONZALEZ MIQUEO.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: FIMA 2021 GN PROYECTOS ESTRATEGICOS DE I+D 2021-2024
    Fecha de inicio: 01-05-2021
    Fecha fin: 29-02-2024
    Importe concedido: 758.651,29€
    Otros fondos: -
  • Título: Estudio genómico para la personalización del diagnóstico y el tratamiento de los pacientes con insuficiencia Cardíaca crónica y enfermedad renal crónica (Medicina cardIoreNal pERsonalizada en NaVArra)-II (MINERVA-II)
    Código de expediente: 0011-1411-2021-000094
    Investigador principal: JUAN JOSE GAVIRA GOMEZ.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2021 GN PROYECTOS ESTRATEGICOS DE I+D 2021-2024
    Fecha de inicio: 01-05-2021
    Fecha fin: 29-02-2024
    Importe concedido: 100.748,76€
    Otros fondos: -
  • Título: Aplicaciones del estudio multi-ómico de la microbiota al desarrollo de soluciones biotecnológicas innovadoras en el área de la salud (microBiomics)
    Código de expediente: 0011-1411-2021-000106
    Investigador principal: MARIA TERESA HERRAIZ BAYOD, MARIA TERESA HERRAIZ BAYOD, MARIA TERESA HERRAIZ BAYOD.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2021 GN PROYECTOS ESTRATEGICOS DE I+D 2021-2024
    Fecha de inicio: 15-04-2021
    Fecha fin: 29-02-2024
    Importe concedido: 366.577,17€
    Otros fondos: -
  • Título: Papel de los mecanimso de regulación trascripcional en la patogenia y el tratamiento de los SMD
    Código de expediente: PI20/01308
    Investigador principal: FELIPE LUIS PROSPER CARDOSO.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2020 AES Proyectos de investigación
    Fecha de inicio: 01-01-2021
    Fecha fin: 31-12-2024
    Importe concedido: 275.880,00€
    Otros fondos: Fondos FEDER
  • Título: Periostio mimético: mecanismos de reparación ósea y potencial terapéutico
    Código de expediente: PI20/00076
    Investigador principal: FROILAN GRANERO MOLTO.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2020 AES Proyectos de investigación
    Fecha de inicio: 01-01-2021
    Fecha fin: 31-12-2023
    Importe concedido: 123.420,00€
    Otros fondos: Fondos FEDER
  • Título: Nuevos biomarcadores inmunes para la identificación de grupos de riesgo de sufrir infección grave por COVID¿19 mediante citometría de flujo
    Código de expediente: 0011-3638-2020-000004
    Investigador principal: JOSE RAMON YUSTE ARA.
    Financiador: GOBIERNO DE NAVARRA. DEPARTAMENTO DE SALUD
    Convocatoria: 2020 GN Proyectos de Investigación en salud
    Fecha de inicio: 21-12-2020
    Fecha fin: 20-12-2021
    Importe concedido: 34.500,00€
    Otros fondos: Fondos FEDER
  • Título: Studying the Effect of the Presence of Clonal Hematopoiesis on the Pathogenesis of COVID-19
    Código de expediente: 0011-3638-2020-000011
    Investigador principal: BORJA SAEZ OCHOA.
    Financiador: GOBIERNO DE NAVARRA. DEPARTAMENTO DE SALUD
    Convocatoria: FIMA 2020 PROYECTOS DE I+D EN SALUD CONVOCATORIA ESPECÍFICA COVID19
    Fecha de inicio: 21-12-2020
    Fecha fin: 20-12-2021
    Importe concedido: 34.999,10€
    Otros fondos: Fondos FEDER
  • Título: IDENTIFICATION OF NEW MOLECULAR TARGETS INVOLVED IN THE DEVELOPMENT OF ADVERSE CARDIAC REMODELING
    Código de expediente: 0011-0537-2019-000012
    Investigador principal: LAURA PILAR AGUADO ALVARO.
    Financiador: GOBIERNO DE NAVARRA / DPTO. EDUCACIÓN CULTURA Y TURISMO
    Convocatoria: FIMA GNE 2019 BECAS PREDOCTORALES
    Fecha de inicio: 01-12-2020
    Fecha fin: 30-04-2022
    Importe concedido: 33.240,87€
    Otros fondos: -
  • Título: FPU 2019 PAULA RODRIGUEZ MÁRQUEZ JRRM-JJL
    Código de expediente: FPU19/06160
    Investigador principal: PAULA RODRIGUEZ MARQUEZ.
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: FIMA 2019 - MINECO BECAS FPU FIMA 2019 - MINECO BECAS FPU
    Fecha de inicio: 15-10-2020
    Fecha fin: 02-12-2022
    Importe concedido: 60.268,98€
    Otros fondos: Fondos FEDER
  • Título: Alianza en Genómica Avanzada para el desarrollo de Terapias Personalizadas en Navarra
    Código de expediente: 0011-1411-2020-000010
    Investigador principal: FELIPE LUIS PROSPER CARDOSO.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: FIMA 2020 GN PROYECTOS ESTRATEGICOS DE I+D 2020-2022
    Fecha de inicio: 17-06-2020
    Fecha fin: 30-11-2022
    Importe concedido: 725.480,08€
    Otros fondos: -
  • Título: Transcriptional and gene regulatory networks in acute myeloid leukemia secondary to myelodysplastic syndromes: identification of novel therapeutic targets
    Código de expediente: 0011-0537-2019-000001
    Investigador principal: NEREA BERASTEGUI ZUFIAURRE.
    Financiador: GOBIERNO DE NAVARRA / DPTO. EDUCACIÓN CULTURA Y TURISMO
    Convocatoria: FIMA GNE 2019 BECAS PREDOCTORALES
    Fecha de inicio: 01-06-2020
    Fecha fin: 01-10-2023
    Importe concedido: 68.715,96€
    Otros fondos: -
  • Título: Incapacitación de las células endógenas del tejido cardiaco dañado para aumentar el injerto de los progenitores cardiovasculares trasplantados
    Código de expediente: PID2019-107150RB-I00
    Investigador principal: XONIA CARVAJAL VERGARA.
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: FIMA 2019 MCIU - AEI PROYECTOS DE I+D RETOS INVESTIGACION
    Fecha de inicio: 01-06-2020
    Fecha fin: 22-11-2021
    Importe concedido: 121.000,00€
    Otros fondos: Fondos FEDER
  • Título: Quimerismo inter-especie y edición génica en embriones de cerdo: QuimPig
    Código de expediente: 0011-1365-2020-000293
    Investigador principal: XABIER ARANGUREN LOPEZ.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: FIMA 2020 GN I+D EMPRESAS (Transferencia del conocimiento 2020) QuimPig
    Fecha de inicio: 01-04-2020
    Fecha fin: 30-07-2022
    Importe concedido: 172.973,35€
    Otros fondos: Fondos FEDER
  • Título: IDENTIFICACIÓN Y DESARROLLO DE TCR TRANSGÉNICOS PARA TERAPIA CELULAR ADOPTIVA DE TUMORES SÓLIDOS
    Código de expediente: 0011-1383-2020-000010 PC197
    Investigador principal: SUSANA INMACULADA INOGES SANCHO.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2020 GN Proyectos Colaborativos
    Fecha de inicio: 01-12-2019
    Fecha fin: 30-11-2022
    Importe concedido: 137.325,00€
    Otros fondos: -
  • Título: Desarrollo y evaluación de inmunoterapia celular mediante CART alogénicas para el tratamiento de la Leucemia Mieloide Aguda
    Código de expediente: 0011-1383-2020-000013
    Investigador principal: JUAN ROBERTO RODRIGUEZ MADOZ.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: FIMA 2020 - GN INDUSTRIA PROYECTOS CENTROS TECNOLOGICOS Y ORGANISMOS DE INVESTIGACION
    Fecha de inicio: 01-12-2019
    Fecha fin: 30-11-2022
    Importe concedido: 123.668,75€
    Otros fondos: -
  • Título: IJCI-2017-33070 GIULIA COPPIELLO FP
    Código de expediente: IJCI-2017-33070
    Investigador principal: GIULIA COPPIELLO .
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: 2017 - JUAN DE LA CIERVA INCORPORACION 2017 - JUAN DE LA CIERVA INCORPORACION
    Fecha de inicio: 01-04-2019
    Fecha fin: 31-08-2021
    Importe concedido: 76.156,16€
    Otros fondos: Fondos FEDER
  • Título: Ecosystem of hematopoietic stem cell: Manipulation of the niche for therapeutic use
    Código de expediente: 0011-0537-2018-000008
    Investigador principal: ANA CRISTINA VIÑADO SOLANAS.
    Financiador: GOBIERNO DE NAVARRA / DPTO. EDUCACIÓN CULTURA Y TURISMO
    Convocatoria: GNE 2018 BECAS PREDOCTORALES
    Fecha de inicio: 01-04-2019
    Fecha fin: 31-03-2022
    Importe concedido: 68.718,00€
    Otros fondos: -
  • Título: Caracterización bioinformática, del perfil transcriptómico y epigenético de células madre hematopoyéticas (CD34+). Integración de ambas tecnologías genómicas para identificar "gene regulatory networks"
    Código de expediente:
    Investigador principal: MARINA AINCIBURU FERNANDEZ.
    Financiador: GOBIERNO DE NAVARRA / DPTO. EDUCACIÓN CULTURA Y TURISMO
    Convocatoria: GNE 2018 BECAS PREDOCTORALES
    Fecha de inicio: 01-04-2019
    Fecha fin: 08-09-2019
    Importe concedido: 68.718,00€
    Otros fondos: Fondos FEDER
  • Título: Desarrollo de estructuras 3D para igeniería de tejidos
    Código de expediente: 0011-1383-2019-000005 PC074
    Investigador principal: FROILAN GRANERO MOLTO.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2019 GN Centros
    Fecha de inicio: 01-02-2019
    Fecha fin: 30-11-2019
    Importe concedido: 45.552,13€
    Otros fondos: -
  • Título: Hacia la generación de xeno-órganos mediante complementación de blastocisto (XenoOrgan)
    Código de expediente: RTI2018-094485-B-I00
    Investigador principal: XABIER ARANGUREN LOPEZ.
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: 2018 - PROYECTOS DE I+D RETOS INVESTIGACION
    Fecha de inicio: 01-01-2019
    Fecha fin: 30-06-2022
    Importe concedido: 145.200,00€
    Otros fondos: Fondos FEDER
  • Título: Impulsando la cooperación hacia la innovación en el tratamiento de las enfermedades cardiovasculares: nuevas terapias regenerativas para el infarto de miocardio
    Código de expediente: 2019/3
    Investigador principal: BEATRIZ PELACHO SAMPER.
    Financiador: EURORREGIÓN AQUITANIA-EUSKADI-NAVARRA
    Convocatoria: Nueva Aquitania Euskadi Navarra 2018
    Fecha de inicio: 20-12-2018
    Fecha fin: 20-06-2020
    Importe concedido: 23.817,50€
    Otros fondos: -
  • Título: Inhibidores epigenéticos e impresión 3D para lesiones tendinomusculares.
    Código de expediente: 0011-1383-2019-000006
    Investigador principal: ANA ISABEL PEREZ RUIZ.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2019 - GN INDUSTRIA PROYECTOS CENTROS TECNOLOGICOS Y ORGANISMOS DE INVESTIGACION
    Fecha de inicio: 01-12-2018
    Fecha fin: 30-11-2019
    Importe concedido: 126.096,23€
    Otros fondos: -
  • Título: Terapia basada en RNA mediante quimeras aptámero-siRNAs contra lncRNAs en el mieloma múltiple. RTHALMY
    Código de expediente: SAF2017-92632-EXP
    Investigador principal: FELIPE LUIS PROSPER CARDOSO.
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: 2017 - PROYECTOS EXPLORA CIENCIA Y EXPLORA TECNOLOGIA
    Fecha de inicio: 01-11-2018
    Fecha fin: 31-12-2020
    Importe concedido: 84.700,00€
    Otros fondos: Fondos FEDER
  • Título: Estudio genómico para la personalización del diagnóstico y el tratamiento de los pacientes con insuficiencia cardiaca crónica y enfermedad renal crónica (Medicina cardIoreNal pERsonalizada en NaVArra) (MINERVA)
    Código de expediente: 0011-1411-2018-000036
    Investigador principal: JUAN JOSE GAVIRA GOMEZ.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2018 GN PROYECTOS ESTRATEGICOS DE I+D 2018-2020
    Fecha de inicio: 01-04-2018
    Fecha fin: 30-11-2020
    Importe concedido: 97.237,60€
    Otros fondos: -
  • Título: Tecnología 3D en bioingeniería de tejidos para generación de un miocardio humano maduro
    Código de expediente: 0011-1383-2018-000011
    Investigador principal: MANUEL MARIA MAZO VEGA.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2018 - GN INDUSTRIA PROYECTOS CENTROS TECNOLOGICOS Y ORGANISMOS DE INVESTIGACION
    Fecha de inicio: 01-02-2018
    Fecha fin: 30-11-2018
    Importe concedido: 149.604,75€
    Otros fondos: -
  • Título: Estudio de la arquitectura genómica y transcripcional en SMDs como herramienta para la determinación de factores pronósticos y nuevas dianas terapeúticas.
    Código de expediente: PI17/00701
    Investigador principal: FELIPE LUIS PROSPER CARDOSO.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: AES2017 PROYECTOS DE INVESTIGACIÓN
    Fecha de inicio: 01-01-2018
    Fecha fin: 31-12-2020
    Importe concedido: 209.330,00€
    Otros fondos: Fondos FEDER
  • Título: Desarrollo de nuevos regímenes de acondicionamiento no genotóxico para el trasplante de progenitores hematopoyéticos en hemoglobinopatías congénitas y enfermedades autoinmunes.
    Código de expediente: PI17/01346
    Investigador principal: BORJA SAEZ OCHOA.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2017 - PROYECTOS DE I+D EN SALUD
    Fecha de inicio: 01-01-2018
    Fecha fin: 31-12-2020
    Importe concedido: 129.470,00€
    Otros fondos: Fondos FEDER
  • Título: ENTENDIENDO EL PAPEL DE LAS CELULAS MADRE DE PULMON EN LA REGULACION DE LA FIBROSIS PULMONAR PARA EL DESARROLLO DE NUEVAS TERAPIAS REGENERATIVAS.
    Código de expediente: SAF2017-89908-R
    Investigador principal: ANA PARDO SAGANTA.
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: 2017 MINECO RETOS
    Fecha de inicio: 01-01-2018
    Fecha fin: 31-12-2021
    Importe concedido: 171.094,00€
    Otros fondos: Fondos FEDER
  • Título: Seudoartrois de fractura y estrés oxidativo: optimización de autoinjertos óseos miméticos y mecanismo molecular.
    Código de expediente: PI17/00136
    Investigador principal: FROILAN GRANERO MOLTO.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: AES2017 PROYECTOS DE INVESTIGACIÓN
    Fecha de inicio: 01-01-2018
    Fecha fin: 31-12-2020
    Importe concedido: 105.270,00€
    Otros fondos: Fondos FEDER
  • Título: MINECO - IJCI-2015-23390
    Código de expediente: IJCI-2015-23390
    Investigador principal: ISABEL CALVO ARNEDO.
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: 2015 - JUAN DE LA CIERVA INCORPORACION
    Fecha de inicio: 01-02-2017
    Fecha fin: 30-01-2018
    Importe concedido: 64.000,00€
    Otros fondos: Fondos FEDER
  • Título: Red de Terapia Celular (TerCel)
    Código de expediente: RD16/0011/0005
    Investigador principal: FELIPE LUIS PROSPER CARDOSO.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2016 AES REDES
    Fecha de inicio: 01-01-2017
    Fecha fin: 30-12-2022
    Importe concedido: 307.285,00€
    Otros fondos: -
  • Título: Estudio de la respuesta inmune inducida por vacunas de células dendríticas autólogas en pacientes con cáncer de mama para el desarrollo de nuevas estrategias terapéuticas.
    Código de expediente: PI16/01245
    Investigador principal: MARTA SANTISTEBAN ESLAVA, SUSANA INMACULADA INOGES SANCHO.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2016 AES PROYECTOS DE INVESTIGACIÓN
    Fecha de inicio: 01-01-2017
    Fecha fin: 31-12-2019
    Importe concedido: 96.800,00€
    Otros fondos: Fondos FEDER
  • Título: Tratamiento del infarto de miocardio y prevención del remodelado adverso mediante la aplicación de factores de crecimiento y microRNAs anti-fibróticos
    Código de expediente: PI16/00129
    Investigador principal: BEATRIZ PELACHO SAMPER, JUAN JOSE GAVIRA GOMEZ.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2016 - PROYECTOS DE I+D EN SALUD
    Fecha de inicio: 01-01-2017
    Fecha fin: 30-06-2020
    Importe concedido: 98.615,00€
    Otros fondos: Fondos FEDER
  • Título: Potencial de la edición génica in vivo mediante CRISPR/Cas para el tratamiento y modelado de Hiperoxaluria Primaria
    Código de expediente: PI16/00150
    Investigador principal: JUAN ROBERTO RODRIGUEZ MADOZ.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2016 - PROYECTOS DE I+D EN SALUD
    Fecha de inicio: 01-01-2017
    Fecha fin: 31-12-2020
    Importe concedido: 80.465,00€
    Otros fondos: Fondos FEDER
  • Título: UTILIZACIÓN DE MEMBRANAS DE COLÁGENO COMO MATRICES PARA REGENERACIÓN DE TEJIDOS
    Código de expediente: 0011-1408-2016-000003
    Investigador principal: IÑIGO PEREZ ESTENAGA.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2016 -GN DOCTORANDOS INDUSTRIALES 2017- 2019
    Fecha de inicio: 01-01-2017
    Fecha fin: 31-12-2019
    Importe concedido: 85.012,50€
    Otros fondos: -
  • Título: Inducción de Tolerancia con células dendríticas tratadas con vitamina d3 y cargadas de mielina, en pacientes con esclerosis múltiple.
    Código de expediente: PI16/01797
    Investigador principal: ASCENSION LOPEZ DIAZ DE CERIO.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2016 AES PROYECTOS DE INVESTIGACIÓN
    Fecha de inicio: 01-01-2017
    Fecha fin: 31-12-2019
    Importe concedido: 55.055,00€
    Otros fondos: Fondos FEDER
  • Título: Estudio del potencial de los progenitores cardiovasculares inducidos en modelos de infarto de miocardio.
    Código de expediente: SAF2016-79398-R
    Investigador principal: XONIA CARVAJAL VERGARA.
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: 2016 - PROYECTOS DE I+D RETOS
    Fecha de inicio: 30-12-2016
    Fecha fin: 29-04-2020
    Importe concedido: 157.300,00€
    Otros fondos: Fondos FEDER
  • Título: Understanding the role of lung stem cells in pulmonary fibrosis
    Código de expediente:
    Investigador principal: ANA PARDO SAGANTA.
    Financiador: GOBIERNO DE NAVARRA. DEPARTAMENTO DE SALUD
    Convocatoria: 2016 PROYECTOS DE I+D EN SALUD
    Fecha de inicio: 09-12-2016
    Fecha fin: 08-12-2019
    Importe concedido: 64.316,05€
    Otros fondos: Fondos FEDER
  • Título: POTENCIAL DE LA EDICIÓN GÉNICA IN VIVO MEDIANTE CRISPR/Cas PARA EL TRATAMIENTO DE HIPEROXALURIA PRIMARIA
    Código de expediente:
    Investigador principal: JUAN ROBERTO RODRIGUEZ MADOZ.
    Financiador: GOBIERNO DE NAVARRA. DEPARTAMENTO DE SALUD
    Convocatoria: 2016 PROYECTOS DE I+D EN SALUD
    Fecha de inicio: 09-12-2016
    Fecha fin: 08-12-2019
    Importe concedido: 54.964,25€
    Otros fondos: Fondos FEDER
  • Título: MINECO RYC-2015-17233
    Código de expediente: RYC-2015-17233
    Investigador principal: XABIER ARANGUREN LOPEZ.
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: 2015 - MINECO RAMON Y CAJAL FIMA 2022 MINECO I3 2015 - MINECO RAMON Y CAJAL
    Fecha de inicio: 01-12-2016
    Fecha fin: 03-06-2024
    Importe concedido: 322.549,92€
    Otros fondos: Fondos FEDER
  • Título: MINECO RYC-2015-18580
    Código de expediente: RYC-2015-18580
    Investigador principal: ANA PARDO SAGANTA.
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: 2015 - MINECO RAMON Y CAJAL
    Fecha de inicio: 01-12-2016
    Fecha fin: 22-03-2022
    Importe concedido: 208.600,00€
    Otros fondos: Fondos FEDER
  • Título: Nanopartículas de esqualeno-adenosina para el tratamiento de la isquemia-reperfusión cardiaca
    Código de expediente: PCIN-2016-046
    Investigador principal: MARIA JOSE BLANCO PRIETO.
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: 2016 MINECO ACCIONES DE PROGRAMACIÓN CONJUNTA INTERNACIONAL
    Fecha de inicio: 01-05-2016
    Fecha fin: 31-12-2020
    Importe concedido: 98.000,00€
    Otros fondos: -
  • Título: Desarrollo clínico de una terapia celular para reparación cardíaca basada en ingeniería de tejidos-CARDIOMESH
    Código de expediente: RTC-2016-4911-1
    Investigador principal: FELIPE LUIS PROSPER CARDOSO.
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: 2016 MINECO RETOS-COLABORACION
    Fecha de inicio: 09-03-2016
    Fecha fin: 28-02-2019
    Importe concedido: 222.982,00€
    Otros fondos: -
  • Título: CONTRATO MIGUEL SERVET TIPO II Beatriz pelacho
    Código de expediente: MSII15/00017
    Investigador principal: BEATRIZ PELACHO SAMPER.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2015 CONTRATOS DE ESTABILIZACION DE DOCTORES MIGUEL SERVET TIPO II
    Fecha de inicio: 01-03-2016
    Fecha fin: 31-01-2019
    Importe concedido: 87.750,00€
    Otros fondos: Fondos FEDER
  • Título: Biomateriales y nanopartículas para la aplicación y liberación de células y proteínas terapéuticas para la reparación del corazón (EURONANOMED-036)
    Código de expediente: AC15/00050
    Investigador principal: FELIPE LUIS PROSPER CARDOSO, FELIPE LUIS PROSPER CARDOSO.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2015 AES ACCIONES COMPLEMENTARIAS
    Fecha de inicio: 01-01-2016
    Fecha fin: 30-06-2019
    Importe concedido: 149.435,00€
    Otros fondos: -
  • Título: Endotelización inter-especies como estrategia para la realización de Xenotrasplantes
    Código de expediente: SAF2015-064224-R
    Investigador principal: XABIER ARANGUREN LOPEZ.
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: 2015 - PROYECTOS DE I+D RETOS
    Fecha de inicio: 01-01-2016
    Fecha fin: 30-06-2019
    Importe concedido: 116.800,00€
    Otros fondos: Fondos FEDER
  • Título: Understanding primary hyperoxaluria type 1 towards the development of innovative therapeutic strategies (ERARE)
    Código de expediente: AC15/00036
    Investigador principal: FELIPE LUIS PROSPER CARDOSO.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2015 AES ACCIONES COMPLEMENTARIAS
    Fecha de inicio: 01-01-2016
    Fecha fin: 31-12-2019
    Importe concedido: 99.946,00€
    Otros fondos: -
  • Título: Endotelizacion inter-especies como estrategia para la realizacion de Xenotrasplantes (IntereXt)
    Código de expediente: 31/2015
    Investigador principal: XABIER ARANGUREN LOPEZ.
    Financiador: GOBIERNO DE NAVARRA. DEPARTAMENTO DE SALUD
    Convocatoria: 2015 PROYECTOS DE I+D EN SALUD
    Fecha de inicio: 06-12-2015
    Fecha fin: 05-12-2018
    Importe concedido: 41.760,00€
    Otros fondos: Fondos FEDER
  • Título: Nuevas dianas epigenáticas en mieloma múltiple
    Código de expediente: FPU2014-04331
    Investigador principal: RAQUEL ORDOÑEZ CIRIZA.
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: 2014 - MINECO BECAS FPU
    Fecha de inicio: 01-10-2015
    Fecha fin: 30-09-2018
    Importe concedido: 59.200,00€
    Otros fondos: Fondos FEDER
  • Título: Reprogramación cardíaca in vitro e in vivo por factores definidos como estrategia de regeneración cardíaca
    Código de expediente: BES2014-069226
    Investigador principal: JAVIER LINARES ACOSTA.
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: 2013 - MINECO FPI
    Fecha de inicio: 24-03-2015
    Fecha fin: 23-03-2019
    Importe concedido: 83.900,00€
    Otros fondos: Fondos FEDER
  • Título: Inhibición de la actividad metiltransferasa de G9a mediante moléculas pequeñas como estrategia terapéutica en tumores hematológicos
    Código de expediente: PI14/01867
    Investigador principal: FELIPE LUIS PROSPER CARDOSO.
    Financiador: INSTITUTO DE SALUD CARLOS III
    Convocatoria: 2014 - PROYECTOS DE I+D EN SALUD
    Fecha de inicio: 01-01-2015
    Fecha fin: 30-06-2018
    Importe concedido: 207.515,00€
    Otros fondos: Fondos FEDER
  • Título: Ramón y Cajal Convocatoria 2012
    Código de expediente: RYC-2012-10981
    Investigador principal: XONIA CARVAJAL VERGARA.
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: 2012 - MINECO RAMON Y CAJAL
    Fecha de inicio: 04-11-2013
    Fecha fin: 11-08-2019
    Importe concedido: 208.600,00€
    Otros fondos: Fondos FEDER
  • Título: Targeted NANOmedicine to reverse FIBrosis in ischemic cardiomyopathies
    Código de expediente:
    Investigador principal: BEATRIZ PELACHO SAMPER
    Financiador: AGENCIA ESTATAL DE INVESTIGACION
    Convocatoria: M-ERA.NET Call 2022
    Fecha de inicio: 15-10-2023
    Fecha fin: 14-10-2026
    Importe concedido: 124.630,00€
    Otros fondos: -
  • Título: Hijacking stroma antigens for CAR-T cell immunotherapy of PDAC
    Código de expediente: TRNSC235655PINE
    Investigador principal: ANTONIO ANGEL PINEDA LUCENA
    Financiador: ASOCIACION ESPAÑOLA CONTRA EL CANCER
    Convocatoria: TRANSCAN-3 JTC 2022
    Fecha de inicio: 15-10-2023
    Fecha fin: 14-10-2026
    Importe concedido: 110.000,00€
    Otros fondos: -
  • Título: Dissecting the role of the immune microenvironment in the onset of myelodysplastic syndromes
    Código de expediente: 101110212
    Investigador principal: IRENE GAÑAN GOMEZ IRENE GAÑAN GOMEZ
    Financiador: COMISIÓN EUROPEA
    Convocatoria: HORIZON-MSCA-2022-PF-01
    Fecha de inicio: 01-09-2023
    Fecha fin: 31-08-2025
    Importe concedido: 181.152,96€
    Otros fondos: -
  • Título: Advanced bioengineering of an all-human platform to study transthyretin amyloid cardiomyopathy
    Código de expediente: 67562235
    Investigador principal: OLALLA Iglesias GARCIA
    Financiador: PFIZER INC
    Convocatoria: Junior Investigator ATTR-CM Research
    Fecha de inicio: 01-01-2022
    Fecha fin: 31-12-2023
    Importe concedido: 127.360,00€
    Otros fondos: -
  • Título: T2EVOVLE - Accelerating Development and Improving Access to CAR and TCR
    Código de expediente:
    Investigador principal: FELIPE LUIS PROSPER CARDOSO
    Financiador: COMISIÓN EUROPEA
    Convocatoria: H2020-JTI-IMI2-2019-18
    Fecha de inicio: 01-01-2021
    Fecha fin: 31-12-2025
    Importe concedido: 271.370,00€
    Otros fondos: -
  • Título: Red de Excelencia para el desarrollo de Terapias Avanzadas de tratamiento del Infarto de Miocardio basadas en medicina regenerativa e impresión 3D
    Código de expediente: SOE4/P1/E0163
    Investigador principal: BEATRIZ PELACHO SAMPER
    Financiador: MINISTERIO DE HACIENDA
    Convocatoria: SUDOE 4/P1
    Fecha de inicio: 01-09-2020
    Fecha fin: 30-04-2023
    Importe concedido: 123.750,00€
    Otros fondos: -
  • Título: Red de Excelencia para el desarrollo de Terapias Avanzadas de tratamiento del Infarto de Miocardio basadas en medicina regenerativa e impresión 3D
    Código de expediente: SOE4/P1/E1063
    Investigador principal: FELIPE LUIS PROSPER CARDOSO
    Financiador: INTERREG SUDOE
    Convocatoria: INTERREG SUDOE 4ª convocatoria
    Fecha de inicio: 01-09-2020
    Fecha fin: 30-04-2023
    Importe concedido: 150.000,00€
    Otros fondos: Fondos FEDER
  • Título: HEALIKICK - A modular strategy for the repair of critical sized bone fractures
    Código de expediente: 874889
    Investigador principal: FROILAN GRANERO MOLTO
    Financiador: COMISIÓN EUROPEA
    Convocatoria: SC1-BHC-07-2019: Regenerative medicine: from new insights to new applications
    Fecha de inicio: 01-06-2020
    Fecha fin: 31-05-2025
    Importe concedido: 569.375,00€
    Otros fondos: -
  • Título: MEPHOS - Shaping the Mechano-Pharmacological properties of Microparticles and Extracellular Vesicles for the Treatment of Osteoarthritis
    Código de expediente:
    Investigador principal: FELIPE LUIS PROSPER CARDOSO
    Financiador: COMISIÓN EUROPEA
    Convocatoria: H2020-MSCA-RISE-2019
    Fecha de inicio: 01-04-2020
    Fecha fin: 31-03-2024
    Importe concedido: 257.600,00€
    Otros fondos: -
  • Título: BRAV3: Computational biomechanics and bioengineering 3D printing to develop a personalized regenerative biological ventricular assist device to provide lasting functional support to damaged hearts
    Código de expediente: 874827
    Investigador principal: FELIPE LUIS PROSPER CARDOSO
    Financiador: COMISIÓN EUROPEA
    Convocatoria: SC1-BHC-07-2019: Regenerative medicine: from new insights to new applications
    Fecha de inicio: 01-01-2020
    Fecha fin: 31-12-2024
    Importe concedido: 800.500,00€
    Otros fondos: -
  • Título: LGMed: La tecnología a servicio de la salud: desarrollo de dispositivos médicos de última generación
    Código de expediente: EFA313/19
    Investigador principal: FELIPE LUIS PROSPER CARDOSO
    Financiador: POCTEFA
    Convocatoria: 3ª convocatoria de proyectos POCTEFA 2014-2020
    Fecha de inicio: 01-11-2019
    Fecha fin: 31-05-2022
    Importe concedido: 144.469,00€
    Otros fondos: Fondos FEDER
  • Título: EHA Research Mobility Grant Alvaro Sanchez Herreros
    Código de expediente:
    Investigador principal: ALVARO SANCHEZ HERRERO
    Financiador: European Hematology Association (EHA)
    Convocatoria: EHA Research Mobility Grants 2018
    Fecha de inicio: 12-12-2018
    Fecha fin: 11-03-2019
    Importe concedido: 6.660,00€
    Otros fondos: -
  • Título: Early detection and intervention: Understanding the mechanisms of transformation and hidden resistance of incurable haematological malignancies
    Código de expediente: C355/A26819
    Investigador principal: JESUS FERNANDO SAN MIGUEL IZQUIERDO
    Financiador: ASOCIACION ESPAÑOLA CONTRA EL CANCER
    Convocatoria: Accelerator Grant 2017
    Fecha de inicio: 01-12-2018
    Fecha fin: 30-11-2023
    Importe concedido: 764.889,66€
    Otros fondos: -
  • Título: RESTORE - Neuronal Self-Renewal by antigen-specific Tolerization in Multiple Sclerosis reinstalling the balance between inflamation and regeneration
    Código de expediente:
    Investigador principal: FELIPE LUIS PROSPER CARDOSO
    Financiador: COMISIÓN EUROPEA
    Convocatoria: H2020-SC1-2017
    Fecha de inicio: 01-01-2018
    Fecha fin: 31-12-2023
    Importe concedido: 625.000,00€
    Otros fondos: -
  • Título: Groundbreaking therapies and disease models for Primary Hyperoxaluria
    Código de expediente:
    Investigador principal: JUAN ROBERTO RODRIGUEZ MADOZ
    Financiador: Oxalosis & Hyperoxaluria Foundation
    Convocatoria: OHF 2016
    Fecha de inicio: 01-10-2017
    Fecha fin: 30-09-2019
    Importe concedido: 160.000,00€
    Otros fondos: -
  • Título: REgenerative therapy of intervertebral disc: a double blind phase 2b trial of intradiscal injection of mesenchymal stromal cells in degenerative disc disease unresponsive to conventional therapy.
    Código de expediente:
    Investigador principal: FELIPE LUIS PROSPER CARDOSO
    Financiador: COMISIÓN EUROPEA
    Convocatoria: H2020-EC-SC1-PM-11-2016
    Fecha de inicio: 01-01-2017
    Fecha fin: 31-12-2022
    Importe concedido: 373.000,00€
    Otros fondos: -
  • Título: PROmuscaging. Role of proteases in muscular homeostasis and aging
    Código de expediente: 19639
    Investigador principal: ANA ISABEL PEREZ RUIZ
    Financiador: AFM TELETHON
    Convocatoria: Research Grant
    Fecha de inicio: 29-04-2016
    Fecha fin: 29-04-2019
    Importe concedido: 60.310,00€
    Otros fondos: -
  • Título: NanoReHeart: MINECO PCIN-2015-200-C02-02 Biomateriales y nanopartículas para mejorar el implante celular y liberación de factores terapéuticos para la regeneración del corazón
    Código de expediente: PCIN-2015-200-C02-02
    Investigador principal: BEATRIZ PELACHO SAMPER
    Financiador: MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES
    Convocatoria: EURONANOMED2
    Fecha de inicio: 01-09-2015
    Fecha fin: 31-03-2019
    Importe concedido: 75.000,00€
    Otros fondos: Fondos FEDER
  • Título: Identification of the epigenomic and transcriptomic alterations in the transformation of benign monoclonal gammapathies to symptomatic multiple myeloma.
    Investigador principal: FELIPE LUIS PROSPER CARDOSO
    Financiador: FUNDACION BBVA
    Convocatoria: 2021 Fundación BBVA Proyectos de investigación
    Fecha de inicio: 01-07-2022
    Fecha fin: 30-06-2024
    Importe concedido: 149.984,50€
  • Título: Molecular mechanisms governing CAR-T cell response in MM patients at single cell level
    Investigador principal: LOREA JORDANA URRIZA
    Financiador: ASOCIACION ESPAÑOLA CONTRA EL CANCER
    Convocatoria: FIMA 2022 Predoctorales AECC
    Fecha de inicio: 15-05-2022
    Fecha fin: 14-02-2023
    Importe concedido: 72.905,55€
  • Título: TOWARDS A NEW PARADIGM IN THE TREATMENT OF BLADDER CARCINOMA: THE COMBINATION OF AN EPIGENETIC AGENT AND AN IMMUNE CHECKPOINT INHIBITOR
    Investigador principal: EDURNE SAN JOSE ENERIZ, EDURNE SAN JOSE ENERIZ
    Financiador: ASOCIACION ESPAÑOLA CONTRA EL CANCER
    Convocatoria: FIMA 2021 Cancer Innova AECC
    Fecha de inicio: 01-10-2021
    Fecha fin: 30-12-2023
    Importe concedido: 180.000,00€
  • Título: Gene Regulatory NETworks in NORmal and MALignant Hematopoiesis- Identification and Targeting (GR-NET NORMAL-HIT
    Investigador principal: FELIPE LUIS PROSPER CARDOSO
    Financiador: FUNDACIÓN BANCARIA LA CAIXA
    Convocatoria: 2020 FD La Caixa Health Research
    Fecha de inicio: 01-12-2020
    Fecha fin: 30-11-2024
    Importe concedido: 411.250,00€
  • Título: Combinatorial Immunotherapies in a novel GEMM platform for sarcomas: Identification of Therapeutic Efficacy and anticipating Adverse Events
    Investigador principal: FERNANDO LECANDA CORDERO
    Financiador: ASOCIACION ESPAÑOLA CONTRA EL CANCER
    Convocatoria: FIMA 2020 Estratégicos AECC
    Fecha de inicio: 01-11-2020
    Fecha fin: 29-02-2024
    Importe concedido: 300.000,00€
  • Título: Desarrollo en micro-bioingeniería humana para detectar y analizar cardiotoxicidad en tratamiento anti-tumoral
    Investigador principal: MANUEL MARIA MAZO VEGA
    Financiador: ASOCIACION ESPAÑOLA CONTRA EL CANCER
    Convocatoria: FIMA Ideas Semilla 2020
    Fecha de inicio: 01-10-2020
    Fecha fin: 30-09-2022
    Importe concedido: 9.700,00€
  • Título: A systems biology approach to reveal the niche composition and connectivity in aging and malignant transformation at the single cell level
    Investigador principal: ITZIAR CENZANO ARMENDARIZ
    Financiador: ASOCIACION ESPAÑOLA CONTRA EL CANCER
    Convocatoria: FIMA 2019 Predoctorales AECC, FIMA 2019 Predoctorales AECC
    Fecha de inicio: 01-12-2019
    Fecha fin: 30-11-2023
    Importe concedido: 91.530,54€
  • Título: Making efficient cells to improve cell therapy transfer for Duchenne muscular dystrophy
    Investigador principal: ANA ISABEL PEREZ RUIZ
    Financiador: ASOCIACION DUCHENNE PARENT PROJECT
    Convocatoria: III Convocatoria de Ayudas a Proyectos de Investigación Duchenne España 2018
    Fecha de inicio: 07-11-2018
    Fecha fin: 06-11-2020
    Importe concedido: 48.000,00€
  • Título: Understanding the interactions between Acute Myeloid Leukemia and their bone marrow niche cells
    Investigador principal: BORJA SAEZ OCHOA
    Financiador: ASOCIACION ESPAÑOLA CONTRA EL CANCER
    Convocatoria: 2016 Ayudas para investigadores en oncología, 2016 Ayudas para investigadores en oncología
    Fecha de inicio: 01-09-2016
    Fecha fin: 30-09-2021
    Importe concedido: 180.000,00€