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Título: | Hypoxia-inducible factor 1 alpha contributes to cardiac healing in mesenchymal stem cells-mediated cardiac repair |
Autor: | Cerrada, Inmaculada; Ruiz-Saurí, Amparo; Carrero, Rubén; Trigueros, César; Dorronsoro, Akaitz CSIC ORCID; Sánchez-Puelles, José María CSIC ORCID ; Díez-Juan, Antonio CSIC ORCID; Montero, Jose Anastasio; Sepúlveda, Pilar | Fecha de publicación: | 14-sep-2012 | Editor: | Mary Ann Liebert | Citación: | Stem Cells Dev. 2013, 22(3) 501-11 | Resumen: | 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-1a) is a master regulator of the adaptative response to hypoxia, we hypothesized that HIF-1a 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-1a 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-1a on MSC biology and suggests the stabilization of HIF-1a as a novel strategy for cellular therapies. | Descripción: | 12 p.-6 fig.-1 tab. | Versión del editor: | http://dx.doi.org/10.1089/scd.2012.0340 | URI: | http://hdl.handle.net/10261/101496 | DOI: | 10.1089/scd.2012.0340 | ISSN: | 1547-3287 | E-ISSN: | 1557-8534 |
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STEMS CELLS AND DEV. Sánchez Puelles.pdf | 521,04 kB | Adobe PDF | Visualizar/Abrir |
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