title: MSCs transfected with hepatocyte growth factor or vascular endothelial growth factor improve cardiac function in the infarcted porcine heart by increasing angiogenesis and reducing fibrosis.
abstract: BACKGROUND
  Cell transplantation and gene therapy have been demonstrated to have beneficial effects after a myocardial infarction (MI). Here, we used a large animal model of MI to investigate the beneficial effects of mesenchymal stem cells (MSCs) transfected with hepatocyte growth factor (HGF) or vascular endothelial growth factor (VEGF) genes.
  
  
  METHODS
  A porcine MI model was created by balloon occlusion of the distal left anterior descending artery for 90 min followed by reperfusion. At 1 week after MI, the pigs were infused via the coronary vein with saline (n=8), MSCs + AdNull(n=8), MSC+VEGF(n=10), or MSC+HGF(n=10). Cardiac function and myocardial perfusion were evaluated by using echocardiography and gated cardiac perfusion imaging before and 4 weeks after transplantation. Morphometric and histological analyses were performed.
  
  
  RESULTS
  All cell-implanted groups had better cardiac function than the saline control group. There were further functional improvements in the MSC+HGF group, accompanied by smaller infarct sizes, increased cell survival, and less collagen deposition. Blood vessel densities in the damaged area and cardiac perfusion were significantly greater in the MSC+AdNull group than in the saline control group, and further increased in the MSC+VEGF/HGF groups. Tissue fibrosis was significantly less extensive in the MSC and MSC+VEGF groups than in the saline control group and was most reduced in the MSC+HGF group.
  
  
  CONCLUSIONS
  MSCs (alone or transfected with VEGF/HGF) delivered into the infarcted porcine heart via the coronary vein improved cardiac function and perfusion, probably by increasing angiogenesis and reducing fibrosis. MSC+HGF was superior to MSC+VEGF, possibly owing to its enhanced antifibrotic effect.
authors.affiliation: Institute of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, PR China.
authors.forename: Fanglin
authors.initials: F
authors.lastname: Lu
authors.forename: Xianxian
authors.initials: X
authors.lastname: Zhao
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Mao
authors.forename: Kebiao
authors.initials: K
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Yuan
authors.forename: Dejun
authors.initials: D
authors.lastname: Gong
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Xu
authors.forename: Shengdong
authors.initials: S
authors.lastname: Huang
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005355:Fibrosis; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000235:genetics*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology; D009203:Myocardial Infarction / Q000235:genetics* / Q000503:physiopathology / Q000601:surgery; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D011897:Random Allocation; D013552:Swine; D014162:Transfection / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor