Abstract |
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.
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Authors | Inmaculada Cerrada, Amparo Ruiz-Saurí, Rubén Carrero, César Trigueros, Akaitz Dorronsoro, Jose María Sanchez-Puelles, Antonio Diez-Juan, Jose Anastasio Montero, Pilar Sepúlveda |
Journal | Stem cells and development
(Stem Cells Dev)
Vol. 22
Issue 3
Pg. 501-11
(Feb 01 2013)
ISSN: 1557-8534 [Electronic] United States |
PMID | 22873764
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cell Adhesion Molecules
- HIF1A protein, human
- Hypoxia-Inducible Factor 1, alpha Subunit
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Topics |
- Animals
- Bone Marrow Cells
(physiology)
- Cell Adhesion
- Cell Adhesion Molecules
(genetics, metabolism)
- Cell Movement
- Cell Survival
- Cells, Cultured
- Coronary Vessels
(physiopathology)
- Heart
(physiopathology)
- Humans
- Hypoxia-Inducible Factor 1, alpha Subunit
(physiology)
- Male
- Mesenchymal Stem Cell Transplantation
- Mesenchymal Stem Cells
(physiology)
- Myocardial Infarction
(pathology, therapy)
- Neovascularization, Physiologic
- Rats
- Rats, Nude
- Regeneration
- Signal Transduction
- Transcriptome
- Up-Regulation
- Wound Healing
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