title: 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.
authors.affiliation: Regenerative Medicine and Heart Transplantation Unit, Fundación para la Investigación Hospital La Fe, Valencia, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Cerrada
authors.forename: Amparo
authors.initials: A
authors.lastname: Ruiz-Saurí
authors.forename: Rubén
authors.initials: R
authors.lastname: Carrero
authors.forename: César
authors.initials: C
authors.lastname: Trigueros
authors.forename: Akaitz
authors.initials: A
authors.lastname: Dorronsoro
authors.forename: Jose María
authors.initials: JM
authors.lastname: Sanchez-Puelles
authors.forename: Antonio
authors.initials: A
authors.lastname: Diez-Juan
authors.forename: Jose Anastasio
authors.initials: JA
authors.lastname: Montero
authors.forename: Pilar
authors.initials: P
authors.lastname: Sepúlveda
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000503:physiopathology; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D018919:Neovascularization, Physiologic; D051381:Rats; D011923:Rats, Nude; D012038:Regeneration; D015398:Signal Transduction; D059467:Transcriptome; D015854:Up-Regulation; D014945:Wound Healing
chemical_list: D015815:Cell Adhesion Molecules; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit