Grupos Investigadores

Líneas de Investigación

  • Terapia celular e ingeniería de tejidos en patología osteoarticular
  • Pathogenic mechanisms of fibrosis and therapeutics strategies for tissue repair (mecanismos patogénicos de la fibrosis y nuevas estrategias terapéuticas)
  • Clinical applications of advanced therapies (Aplicaciones clínicas de las terapias avanzadas)
  • Cardiac Regeneration (Regeneración cardíaca)

Palabras Clave

  • Terapia celular
  • Reprogramación
  • Medicamentos de terapias avanzadas
  • Fibrosis
  • Células madre

Publicaciones Científicas desde 2018

  • 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: 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: 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: 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: 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: 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: 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: 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: 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: Vera Álvarez, Laura; Garcia-Olloqui, P.; 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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); 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: 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: 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: 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: 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: 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: 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: Rosa, S.; Praca, C. ; Pitrez, P. R.; et al.
    Revista: SCIENTIFIC REPORTS
    ISSN 2045-2322 Vol.9 2019
    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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: New targets and designs to improve CAR-T cell based immunotherapy against pancreatic cancer
    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 €
    Fondos FEDER: NO
  • 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: 31-12-2023
    Importe concedido: 100.748,76 €
    Fondos FEDER: NO
  • 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.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2021 GN PROYECTOS ESTRATEGICOS DE I+D 2021-2024
    Fecha de inicio: 15-04-2021
    Fecha fin: 30-11-2023
    Importe concedido: 366.577,17 €
    Fondos FEDER: NO
  • 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: 31-12-2023
    Importe concedido: 275.880,00 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: SI
  • Título: FPU 2019 PAULA RODRIGUEZ MÁRQUEZ JRRM-JJL
    Código de expediente: FPU19/06160
    Investigador principal: PAULA PAULA RODRIGUEZ MARQUEZ MARQUEZ.
    Financiador: MINISTERIO DE CIENCIA E INNOVACIÓN
    Convocatoria: FIMA 2019 - MINECO BECAS FPU FIMA 2019 - MINECO BECAS FPU
    Fecha de inicio: 15-10-2020
    Fecha fin: 15-03-2023
    Importe concedido: 60.268,98 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: NO
  • 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: 01-10-2022
    Importe concedido: 68.715,96 €
    Fondos FEDER: NO
  • 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 E INNOVACIÓN
    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 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: NO
  • Título: IJCI-2017-33070 GIULIA COPPIELLO FP
    Código de expediente: IJCI-2017-33070
    Investigador principal: GIULIA COPPIELLO .
    Financiador: MINISTERIO DE CIENCIA E INNOVACIÓN
    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 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: NO
  • 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 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: NO
  • 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 E INNOVACIÓN
    Convocatoria: 2018 - PROYECTOS DE I+D RETOS INVESTIGACION
    Fecha de inicio: 01-01-2019
    Fecha fin: 30-06-2022
    Importe concedido: 145.200,00 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: NO
  • 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 €
    Fondos FEDER: NO
  • 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 E INNOVACIÓN
    Convocatoria: 2017 - PROYECTOS EXPLORA CIENCIA Y EXPLORA TECNOLOGIA
    Fecha de inicio: 01-11-2018
    Fecha fin: 31-12-2020
    Importe concedido: 84.700,00 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: NO
  • 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 €
    Fondos FEDER: NO
  • 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 €
    Fondos FEDER: SI
  • 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 E INNOVACIÓN
    Convocatoria: 2017 MINECO RETOS
    Fecha de inicio: 01-01-2018
    Fecha fin: 31-12-2021
    Importe concedido: 171.094,00 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: SI
  • Título: MINECO - IJCI-2015-23390
    Código de expediente: IJCI-2015-23390
    Investigador principal: ISABEL CALVO ARNEDO.
    Financiador: MINISTERIO DE CIENCIA E INNOVACIÓN
    Convocatoria: 2015 - JUAN DE LA CIERVA INCORPORACION
    Fecha de inicio: 01-02-2017
    Fecha fin: 30-01-2018
    Importe concedido: 64.000,00 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: NO
  • 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: 30-06-2022
    Importe concedido: 307.285,00 €
    Fondos FEDER: NO
  • 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 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: SI
  • 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 E INNOVACIÓN
    Convocatoria: 2016 - PROYECTOS DE I+D RETOS
    Fecha de inicio: 30-12-2016
    Fecha fin: 29-04-2020
    Importe concedido: 157.300,00 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: SI
  • Título: MINECO RYC-2015-17233
    Código de expediente: RYC-2015-17233
    Investigador principal: XABIER ARANGUREN LOPEZ.
    Financiador: MINISTERIO DE CIENCIA E INNOVACIÓN
    Convocatoria: 2015 - MINECO RAMON Y CAJAL FIMA 2022 MINECO I3 2015 - MINECO RAMON Y CAJAL
    Fecha de inicio: 01-12-2016
    Fecha fin: 03-06-2022
    Importe concedido: 322.549,92 €
    Fondos FEDER: SI
  • Título: MINECO RYC-2015-18580
    Código de expediente: RYC-2015-18580
    Investigador principal: ANA PARDO SAGANTA.
    Financiador: MINISTERIO DE CIENCIA E INNOVACIÓN
    Convocatoria: 2015 - MINECO RAMON Y CAJAL
    Fecha de inicio: 01-12-2016
    Fecha fin: 22-03-2022
    Importe concedido: 208.600,00 €
    Fondos FEDER: SI
  • 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 E INNOVACIÓN
    Convocatoria: 2016 MINECO ACCIONES DE PROGRAMACIÓN CONJUNTA INTERNACIONAL
    Fecha de inicio: 01-05-2016
    Fecha fin: 31-12-2020
    Importe concedido: 98.000,00 €
    Fondos FEDER: NO
  • 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 E INNOVACIÓN
    Convocatoria: 2016 MINECO RETOS-COLABORACION
    Fecha de inicio: 09-03-2016
    Fecha fin: 28-02-2019
    Importe concedido: 222.982,00 €
    Fondos FEDER: NO
  • 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 €
    Fondos FEDER: SI
  • 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 E INNOVACIÓN
    Convocatoria: 2015 - PROYECTOS DE I+D RETOS
    Fecha de inicio: 01-01-2016
    Fecha fin: 30-06-2019
    Importe concedido: 116.800,00 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: NO
  • 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 €
    Fondos FEDER: NO
  • 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 €
    Fondos FEDER: SI
  • Título: Nuevas dianas epigenáticas en mieloma múltiple
    Código de expediente: FPU2014-04331
    Investigador principal: RAQUEL ORDOÑEZ CIRIZA.
    Financiador: MINISTERIO DE CIENCIA E INNOVACIÓN
    Convocatoria: 2014 - MINECO BECAS FPU
    Fecha de inicio: 01-10-2015
    Fecha fin: 30-09-2018
    Importe concedido: 59.200,00 €
    Fondos FEDER: SI
  • 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 E INNOVACIÓN
    Convocatoria: 2013 - MINECO FPI
    Fecha de inicio: 24-03-2015
    Fecha fin: 23-03-2019
    Importe concedido: 83.900,00 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: SI
  • Título: Ramón y Cajal Convocatoria 2012
    Código de expediente: RYC-2012-10981
    Investigador principal: XONIA CARVAJAL VERGARA.
    Financiador: MINISTERIO DE CIENCIA E INNOVACIÓN
    Convocatoria: 2012 - MINECO RAMON Y CAJAL
    Fecha de inicio: 04-11-2013
    Fecha fin: 11-08-2019
    Importe concedido: 208.600,00 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: NO
  • 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 €
    Fondos FEDER: NO
  • 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 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: NO
  • 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 €
    Fondos FEDER: NO
  • 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 €
    Fondos FEDER: NO
  • 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 €
    Fondos FEDER: SI
  • 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 €
    Fondos FEDER: NO
  • 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 €
    Fondos FEDER: NO
  • 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: 31-12-2022
    Importe concedido: 625.000,00 €
    Fondos FEDER: NO
  • 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 €
    Fondos FEDER: NO
  • 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 €
    Fondos FEDER: NO
  • 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 €
    Fondos FEDER: NO
  • 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 E INNOVACIÓN
    Convocatoria: EURONANOMED2
    Fecha de inicio: 01-09-2015
    Fecha fin: 31-03-2019
    Importe concedido: 75.000,00 €
    Fondos FEDER: SI