title: Cell transplantation preserves cardiac function after infarction by infarct stabilization: augmentation by stem cell factor.
abstract: OBJECTIVE
  We hypothesized that implantation of adult mesenchymal stem cells after acute myocardial infarction mobilizes bone marrow precursor cells by activating the stem cell factor pathway, and that overdriving this pathway would enhance the beneficial effects of cell transplantation.
  
  
  METHODS
  After coronary ligation, medium, mesenchymal stem cells, or stem cell factor-overproducing mesenchymal stem cells were injected into the anterior left ventricle. Cells from beta-galactosidase transgenic mice enabled tracking of injected cells. The global and local impact of the cells was evaluated by measuring cytokine levels, endothelial progenitor cells, and myocardial angiogenesis, and by addressing cardiomyogenesis with confocal microscopy. The impact on cardiac function was evaluated by pressure-volume loops. Ventricular morphometrics were measured after in situ perfusion-fixation of the hearts at physiologic pressures.
  
  
  RESULTS
  Implantation of mesenchymal stem cells increased myocardial stem cell factor levels 2.0-fold, endothelial progenitor cell mobilization 2.7-fold, and myocardial angiogenesis 2.3-fold (P < .05), but did not induce mitogenesis in host cardiomyocytes or give rise to beta-galactosidase-expressing cardiomyocytes. Cell-transplanted groups had improved indices of cardiac function, including preload recruitable stroke work and end-systolic elastance (P < .001). Cell transplantation resulted in 2.0-fold smaller ventricular volumes (P = .001) and 2.0-fold reduced infarct scar area (P = .056), but had no effect on the volume of spared myocardium. Stem cell factor overproduction imparted greater functional benefit without inducing detectable histologic cardiomyocyte regeneration.
  
  
  CONCLUSIONS
  Mesenchymal stem cell implantation after myocardial infarction facilitates functional cardiac regeneration without myocyte regeneration through augmentation of endogenous infarct repair, which is enhanced by stem cell factor.
authors.affiliation: Division of Cardiac Surgery, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Shafie
authors.initials: S
authors.lastname: Fazel
authors.forename: Liwen
authors.initials: L
authors.lastname: Chen
authors.forename: Richard D
authors.initials: RD
authors.lastname: Weisel
authors.forename: Denis
authors.initials: D
authors.lastname: Angoulvant
authors.forename: Charit
authors.initials: C
authors.lastname: Seneviratne
authors.forename: Amir
authors.initials: A
authors.lastname: Fazel
authors.forename: Phillip
authors.initials: P
authors.lastname: Cheung
authors.forename: Jason
authors.initials: J
authors.lastname: Lam
authors.forename: Paul W M
authors.initials: PW
authors.lastname: Fedak
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Yau
authors.forename: Ren-Ke
authors.initials: RK
authors.lastname: Li
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000502:physiology; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000601:surgery*; D018919:Neovascularization, Physiologic; D019089:Stem Cell Factor / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology
chemical_list: D019089:Stem Cell Factor