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

Autores de IIS La Fe

• Inmaculada Cerrada Serra

  Autor

• Amparo Ruiz Sauri

  Autor

• Ruben Carrero Garcia

  Autor

• Akaitz Dorronsoro González

  Autor

• Antonio Diez Juan

  Autor

• José Anastasio Montero Argudo

  Autor

• 

  Pilar Sepúlveda Sanchis

  Autor

Participantes ajenos a IIS La Fe

• Trigueros C
• Sanchez-Puelles JM

Grupos

• Regeneración y Trasplante Cardíaco

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-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.