title: A relationship between vascular endothelial growth factor, angiogenesis, and cardiac repair after muscle stem cell transplantation into ischemic hearts.
abstract: OBJECTIVE
  We investigated whether vascular endothelial growth factor (VEGF) was associated with the angiogenic and therapeutic effects induced after transplantation of skeletal muscle-derived stem cells (MDSCs) into a myocardial infarction (MI).
  
  
  BACKGROUND
  Because very few MDSCs were found to differentiate into new blood vessels when injected into the heart, the mechanism underlying the occurrence of angiogenesis after MDSC transplantation is currently unknown. In the present study, we used a gain- or loss-of-VEGF function approach with skeletal MDSCs engineered to express VEGF or soluble Flt1, a VEGF-specific antagonist, to identify the involvement of VEGF in MDSC transplantation-induced neoangiogenesis.
  
  
  METHODS
  Vascular endothelial growth factor- and soluble Flt1-engineered MDSCs were injected into an acute MI. Angiogenesis and cardiac function were evaluated by immunohistochemistry and echocardiography.
  
  
  RESULTS
  Both control and VEGF-overexpressing MDSCs induced angiogenesis, prevented adverse cardiac remodeling, and improved function compared with saline-injected hearts. However, these therapeutic effects were diminished in hearts transplanted with MDSCs expressing soluble Flt1 despite successful cell engraftment. In vitro experiments demonstrated that MDSCs increased secretion of VEGF in response to hypoxia and cyclic stretch (likely conditions in ischemic hearts), suggesting that transplanted MDSCs release VEGF in vivo.
  
  
  CONCLUSIONS
  Our findings suggest that VEGF is essential for the induction of angiogenesis and functional improvements observed after MDSC transplantation for infarct repair.
authors.affiliation: Stem Cell Research Center, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Payne
authors.forename: Hideki
authors.initials: H
authors.lastname: Oshima
authors.forename: Masaho
authors.initials: M
authors.lastname: Okada
authors.forename: Nobuo
authors.initials: N
authors.lastname: Momoi
authors.forename: Kimimasa
authors.initials: K
authors.lastname: Tobita
authors.forename: Bradley B
authors.initials: BB
authors.lastname: Keller
authors.forename: Hairong
authors.initials: H
authors.lastname: Peng
authors.forename: Johnny
authors.initials: J
authors.lastname: Huard
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003326:Coronary Circulation; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018482:Muscle, Skeletal / Q000166:cytology*; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic; D033581:Stem Cell Transplantation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D016277:Ventricular Function, Left
chemical_list: D042461:Vascular Endothelial Growth Factor A