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Hypoxia-inducible factor 1 alpha contributes to cardiac healing in mesenchymal stem cells-mediated cardiac repair.

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.
AuthorsInmaculada Cerrada, Amparo Ruiz-Saurí, Rubén Carrero, César Trigueros, Akaitz Dorronsoro, Jose María Sanchez-Puelles, Antonio Diez-Juan, Jose Anastasio Montero, Pilar Sepúlveda
JournalStem cells and development (Stem Cells Dev) Vol. 22 Issue 3 Pg. 501-11 (Feb 01 2013) ISSN: 1557-8534 [Electronic] United States
PMID22873764 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cell Adhesion Molecules
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
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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