Nuestros investigadores

Xonia Carvajal Vergara

. Fundación para la Investigación Médica Aplicada
Líneas de investigación
Terapia Celular en enfermedades cardiovasculares con células derivadas de células madre de pluripotencia inducida o reprogramación directa.
Índice H
12, (Google Scholar, 29/01/2018)
11, (Scopus, 15/01/2018)
11, (WoS, 27/02/2018)

Publicaciones científicas más recientes (desde 2010)

Autores: Arellano-Viera, E.; Zabaleta, L.; Castano, J. ; et al.
ISSN 1873-5061  Vol. 36  2019 
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:  Lopez-Muneta, L.; Arellano-Viera, E.; Ripalda, Purificación; et al.
ISSN 1873-5061  Vol. 33  2018  págs. 125 - 129
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: Coppiello, G; Abizanda, Gloria María; Aguado, N.; et al.
ISSN 1873-5061  Vol. 21  2017  págs. 1-4
We generated ATCi-MF1 induced pluripotent stem (iPS) cell line from Macaca fascicularis adult skin fibroblasts using non-integrative Sendai viruses carrying OCT3/4, KLF4, SOX2 and c-MYC. Once established, ATCi-MF1 cells present a normal karyotype, are Sendai virus-free and express pluripotency associated markers. Microsatellite markers analysis confirmed the origin of the iPS cells from the parental fibroblasts. Pluripotency was tested with the in vivo teratoma formation assay. ATCi-MF1 cell line may be a useful primate iPS cell model to test different experimental conditions where the use of human cells can imply ethical issues, as microinjection of pluripotent stem cells in pre-implantational embryos.
Autores: Arellano-Viera, E.; et al.
ISSN 1873-5061  Vol. 16  Nº 3  2016  págs. 617 - 621
Mef2c Anterior Heart Field (AHF) enhancer is activated during embryonic heart development and it is expressed in multipotent cardiovascular progenitors (CVP) giving rise to endothelial and myocardial components of the outflow tract, right ventricle and ventricular septum. Here we have generated iPSC from transgenic Mef2c-AHF-Cre x Ai6(RCLZsGreen) mice. These iPSC will provide a novel tool to investigate the AHF-CVP and their cell progeny. (C) 2016 The Authors. Published by Elsevier B.V.
Autores: Munoz-Lopez, A.; Romero-Moya, D.; Prieto, C.; et al.
ISSN 2213-6711  Vol. 7  Nº 4  2016  págs. 602 - 618
Induced pluripotent stem cells (iPSCs) are a powerful tool for disease modeling. They are routinely generated from healthy donors and patients from multiple cell types at different developmental stages. However, reprogramming leukemias is an extremely inefficient process. Few studies generated iPSCs from primary chronic myeloid leukemias, but iPSC generation from acute myeloid or lymphoid leukemias (ALL) has not been achieved. We attempted to generate iPSCs from different subtypes of B-ALL to address the developmental impact of leukemic fusion genes. OKSM(L)-expressing mono/polycistronic-, retroviral/lentiviral/episomal-, and Sendai virus vector-based reprogramming strategies failed to render iPSCs in vitro and in vivo. Addition of transcriptomic-epigenetic reprogramming "boosters'' also failed to generate iPSCs from B cell blasts and B-ALL lines, and when iPSCs emerged they lacked leukemic fusion genes, demonstrating non-leukemic myeloid origin. Conversely, MLL-AF4-overexpressing hematopoietic stem cells/B progenitors were successfully reprogrammed, indicating that B cell origin and leukemic fusion gene were not reprogramming barriers. Global transcriptome/DNA methylome profiling suggested a developmental/differentiation refractoriness of MLL-rearranged B-ALL to reprogramming into pluripotency.
Autores: Lin, B.; Kim, J.; Li, Y. X.; et al.
ISSN 0008-6363  Vol. 95  Nº 3  2012  págs. 327 - 335
A variety of human inherited heart diseases affect the normal functions of cardiomyocytes (CMs), endothelial cells (ECs), or smooth muscle cells (SMCs). To study human heart disease and generate cardiac cells for basic and translational research, an efficient strategy is needed for production of cardiac lineages from human stem cells. In the present study, a highly reproducible method was developed that can simultaneously enrich a large number of CMs and cardiac SMCs and ECs from human induced pluripotent stem (iPS) cells with high purity. Human multipotent cardiovascular progenitor cells were generated from human iPS cells, followed by selective differentiation of the multipotent cardiovascular progenitor cells into CMs, ECs, and SMCs. With further fluorescence-activated cell sorting, each of the three cardiovascular cell types could be enriched with high purity (90). These enriched cardiovascular cells exhibited specific gene expression signatures and normal functions when assayed both in vitro and in vivo. Moreover, CMs purified from iPS cells derived from a patient with LEOPARD syndrome, a disease characterized by cardiac hypertrophy, showed the expected up-regulated expression of genes associated with cardiac hypertrophy. Overall, our technical advance provides the means for generating a renewable resource of pure human cardiovascular cells that can be used to dissect the mechanisms of human inherited heart disease and for the future development of drug and cell therapeutics for heart disease.
Autores: Lee, D. F.; Su, J.; Ang, Y. S.; et al.
ISSN 1934-5909  Vol. 11  Nº 2  2012  págs. 179 - 194
Many signals must be integrated to maintain self-renewal and pluripotency in embryonic stem cells (ESCs) and to enable induced pluripotent stem cell (iPSC) reprogramming. However, the exact molecular regulatory mechanisms remain elusive. To unravel the essential internal and external signals required for sustaining the ESC state, we conducted a short hairpin (sh) RNA screen of 104 ESC-associated phosphoregulators. Depletion of one such molecule, aurora kinase A (Aurka), resulted in compromised self-renewal and consequent differentiation. By integrating global gene expression and computational analyses, we discovered that loss of Aurka leads to upregulated p53 activity that triggers ESC differentiation. Specifically, Aurka regulates pluripotency through phosphorylation-mediated inhibition of p53-directed ectodermal and mesodermal gene expression. Phosphorylation of p53 not only impairs p53-induced ESC differentiation but also p53-mediated suppression of iPSC reprogramming. Our studies demonstrate an essential role for Aurka-p53 signaling in the regulation of self-renewal, differentiation, and somatic cell reprogramming.
Autores: Josowitz, R.; Carvajal-Vergara, Xonia; Lemischka, I. R.; et al.
ISSN 0268-4705  Vol. 26  Nº 3  2011  págs. 223 - 229
Purpose of review The development of induced pluripotent stem cell (iPSC) technology has led to many advances in the areas of directed cell differentiation and characterization. New methods for generating iPSC-derived cardiomyocytes provide an invaluable resource for the study of certain cardiovascular disorders. This review highlights the current technology in this field, its application thus far to the study of genetic disorders of the RAS/MAPK pathway and long-QT syndrome (LQTS), and future directions for the field. Recent findings Enhanced methods increase the efficiency of generating and stringently purifying iPSC-derived cardiomyocytes. The use of cardiomyocytes derived from patients with LEOPARD syndrome and LQTS has shed light on the molecular mechanisms of disease and validated their use as reliable human disease models. Summary The use of iPSC-derived cardiomyocytes to study genetic cardiovascular disorders will enable a deeper and more applicable understanding of the molecular mechanisms of human disease, as well as improving our ability to achieve successful cell-based therapies. Methods to efficiently generate these cells are improving and provide promise for future applications of this technology.
Autores: Carvajal-Vergara, Xonia; Sevilla, A.; D'Souza, S. L.; et al.
Revista: NATURE
ISSN 0028-0836  Vol. 465  Nº 7299  2010  págs. 808 - 812
The generation of reprogrammed induced pluripotent stem cells (iPSCs) from patients with defined genetic disorders holds the promise of increased understanding of the aetiologies of complex diseases and may also facilitate the development of novel therapeutic interventions. We have generated iPSCs from patients with LEOPARD syndrome (an acronym formed from its main features; that is, lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary valve stenosis, abnormal genitalia, retardation of growth and deafness), an autosomal-dominant developmental disorder belonging to a relatively prevalent class of inherited RAS-mitogen-activated protein kinase signalling diseases, which also includes Noonan syndrome, with pleomorphic effects on several tissues and organ systems(1,2). The patient-derived cells have a mutation in the PTPN11 gene, which encodes the SHP2 phosphatase. The iPSCs have been extensively characterized and produce multiple differentiated cell lineages. A major disease phenotype in patients with LEOPARD syndrome is hypertrophic cardiomyopathy. We show that in vitro-derived cardiomyocytes from LEOPARD syndrome iPSCs are larger, have a higher degree of sarcomeric organization and preferential localization of NFATC4 in the nucleus when compared with cardiomyocytes derived from human embryonic stem cells or wild-type iPSCs derived from a healthy brother of one of the LEOPARD syndrome patients. These features correlate with a potential hypertrophic state. We also provide molecular insights into signalling pathways that may promote the disease phenotype.
Autores: Carvajal-Vergara, Xonia; Rodriguez-Madoz, Juan Roberto; Pelacho, Beatriz; et al.
Libro:  Cell therapy: current status and future directions
2017  págs. 173 - 196
The field of regenerative medicine has made great progress with the development of cell reprogramming and gene editing techniques. The option to derive pluripotent cells from somatic cells by overexpression of pluripotent factors or specific molecules, and even more the possibility to reprogram one somatic cell type to another somatic cell type in vitro and in vivo, has offered many new options for future therapies. In this chapter, we provide an overview of the studies performed to understand the mechanisms and to develop the techniques for cell reprogramming, focusing specially in their application in cardiac regeneration and rare disease modeling. First, we discuss the plasticity of cells and methods for their reprogramming. Also, a description of the different studies for differentiation of pluripotent cells toward cardiovascular cells and direct cell reprogramming is provided. Finally, the use of reprogrammed cells as a model for human pathologies, mainly rare diseases, the different aspects that should be bear in mind for optimal model development, the use of gene editing for creating novel and improved disease models, and the therapeutic applications of iPSC-based models have been thoroughly described in this chapter.




Xonia Carvajal-Vergara is Professor of the subject "Basic mechanisms of Cell Therapy" included in Biomedical Research Master at the University of Navarra since 2017.