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San Sebastián de los Reyes, Spain

Rodriguez R.,University of Granada | Garcia-Castro J.,Institute Salud Carlos III | Trigueros C.,Fundacion Inbiomed | Garcia Arranz M.,Hospital Universitario La Paz | Menendez P.,University of Granada
Advances in Experimental Medicine and Biology | Year: 2012

The recognition of the therapeutic potential of Multipotent Mesenchymal Stromal Cells (MSCs) is one of the most exciting recent advances in cell therapy. In just ten years, since the description of the multilineage potential of MSCs by Pittenger et al in 1999 until now, MSCs are being used in more than 150 clinical trials as therapeutic agents. The potential of these cells for cell-based therapies relies on several key properties: (1) their capacity to differentiate into several cell lineages; (2) their lack of immunogenicity and their immunomodulatory properties; (3) their ex vivo expansion potential; (4) their ability to secrete soluble factors which regulate crucial biological functions such as proliferation and differentiation over a broad spectrum of target cells; and (5) their ability to home to damaged tissues and tumor sites. Based on these properties MSCs are being exploited worldwide for a wide range of potential clinical applications including cell replacement strategies, treatment of graft-versus-host disease, autoimmune diseases and rejection after solid organ transplantation as well as their use as vehicles to deliver anti-cancer therapies. Importantly, the low inherent immunogenicity of MSCs means that they could be used not only for autologous but also for allogeneic cell therapies. In addition, increasing evidence has revealed a complex relationship between MSCs and cancer. Thus, solid evidence has placed MSCs transformed with specific mutations as the most likely cell of origin for certain sarcomas, and MSCs have been reported to both, inhibit or promote tumor growth depending on yet undefined conditions. Here we will thoroughly discuss the different potential clinical applications of MSC as well as the role of MSCs on sarcomagenesis and the control of tumor growth. © 2012 Landes Bioscience and Springer Science+Business Media. Source


Arminan A.,Fundacion Para la Investigacion Hospital Universitario la Fe | Arminan A.,Research Center Principe Felipe | Gandia C.,Fundacion Para la Investigacion Hospital Universitario la Fe | Gandia C.,Research Center Principe Felipe | And 12 more authors.
Journal of the American College of Cardiology | Year: 2010

Objectives: The purpose of this study was to compare the ability of human CD34+ hematopoietic stem cells and bone marrow mesenchymal stem cells (MSC) to treat myocardial infarction (MI) in a model of permanent left descendent coronary artery (LDA) ligation in nude rats. Background: Transplantation of human CD34+ cells and MSC has been proved to be effective in treating MI, but no comparative studies have been performed to elucidate which treatment prevents left ventricular (LV) remodelling more efficiently. Methods: Human bone marrow MSC or freshly isolated CD34+ cells from umbilical cord blood were injected intramyocardially in infarcted nude rats. Cardiac function was analyzed by echocardiography. Ventricular remodelling was evaluated by tissue histology and electron microscopy, and neo-formed vessels were quantified by immunohistochemistry. Chronic local inflammatory infiltrates were evaluated in LV wall by hematoxylin-eosin staining. Apoptosis of infarcted tissue was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Results: Both cell types induced an improvement in LV cardiac function and increased tissue cell proliferation in myocardial tissue and neoangiogenesis. However, MSC were more effective for the reduction of infarct size and prevention of ventricular remodelling. Scar tissue was 17.48 ± 1.29% in the CD34 group and 10.36 ± 1.07% in the MSC group (p < 0.001 in MSC vs. CD34). Moreover, unlike MSC, CD34+-treated animals showed local inflammatory infiltrates in LV wall that persisted 4 weeks after transplantation. Conclusions: Mesenchymal stem cells might be more effective than CD34+ cells for the healing of the infarct. This study contributes to elucidate the mechanisms by which these cell types operate in the course of MI treatment. © 2010 American College of Cardiology Foundation. Source


Romero-Camarero I.,University of Salamanca | Barajas-Diego M.,University of Salamanca | Castellanos-Martin A.,University of Salamanca | Garcia-Martin A.,Fundacion Inbiomed | And 5 more authors.
Histology and Histopathology | Year: 2012

Cancer is the subject of intense research around the world, but many questions about how the disease works remain unanswered. How exactly does cancer start and how do tumours grow? In fact, at present there are ten times more anticancer drugs being tested in clinical trials than there were 15 years ago. However, many of the new anticancer agents are predicted to show clinical benefit in only small subpopulations of patients. The cancer stem cell model could explain not only how some cancers work but also why patients suffer relapses, providing a good opportunity to gain insight into the reasons why agents work or, more commonly, don't work, before going into a clinical trial. Source


O'Prey J.,Beatson Institute for Cancer Research | Crighton D.,Beatson Institute for Cancer Research | Martin A.G.,Fundacion Inbiomed | Vousden K.H.,Beatson Institute for Cancer Research | And 2 more authors.
Cell Cycle | Year: 2010

The intricate regulation of cell survival and cell death is critical for the existence of both normal and transformed cells. Two factors central to these processes are p53 and NFκB, with both factors having ascribed roles in both promoting and repressing cell death. Not surprisingly, a number of studies have previously reported interplay between p53 and NFκB. The mechanistic basis behind these observations, however, is currently incomplete. We report here further insights into this interplay using a system where blockade of NFκB inhibits cell death from p53, but at the same time sensitizes cells to death by TNFα. We found in agreement with a recent report showing that NFκB is required for the efficient activation of the BH3-only protein Noxa by the p53 family member p73, that p53's ability to induce Noxa is also impeded by inhibition of NFκB. In contrast to the regulation by p73, however, blockade of NFκB downstream of p53 decreases Noxa protein levels without effects on Noxa mRNA. Our further analysis of the effects of NFκB inhibition on p53 target gene expression revealed that while most target genes analysed where unaffected by blockade of NFκB, the p53-mediated induction of the pro-apoptotic gene p53AIp1 was significantly dependent on NFκB. these studies therefore add further insight into the complex relationship of p53 and NFκB. In addition, since both Noxa and p53AIp1 have been shown to be important components of p53-mediated cell death responses, these findings may also indicate critical points where NFκB plays a pro-apoptotic role downstream of p53. © 2010 Landes Bioscience. Source


Cerrada I.,Regenerative Medicine and Heart Transplantation Unit | Cerrada I.,CEU Cardenal Herrera University | Ruiz-Sauri A.,University of Valencia | Carrero R.,Regenerative Medicine and Heart Transplantation Unit | And 6 more authors.
Stem Cells and Development | Year: 2013

Mesenchymal stem cells (MSC) are effective in treating myocardial infarction (MI) and previous reports demonstrated that hypoxia improves MSC self-renewal and therapeutics. Considering that hypoxia-inducible factor-1 alpha (HIF-1α) is a master regulator of the adaptative response to hypoxia, we hypothesized that HIF-1α overexpression in MSC could mimic some of the mechanisms triggered by hypoxia and increase their therapeutic potential without hypoxia stimulation. Transduction of MSC with HIF-1α lentivirus vectors (MSC-HIF) resulted in increased cell adhesion and migration, and activation of target genes coding for paracrine factors. When MSC-HIF were intramyocardially injected in infarcted nude rats, significant improvement was found (after treatment of infarcted rats with MSC-HIF) in terms of cardiac function, angiogenesis, cardiomyocyte proliferation, and reduction of fibrotic tissue with no induction of cardiac hypertrophy. This finding provides evidences for a crucial role of HIF-1α on MSC biology and suggests the stabilization of HIF-1α as a novel strategy for cellular therapies. © 2013, Mary Ann Liebert, Inc. Source

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