title: HGF and IGF-1 promote protective effects of allogeneic BMSC transplantation in rabbit model of acute myocardial infarction.
abstract: OBJECTIVE
  To explore effects of hepatocyte growth factor (HGF) combined with insulin-like growth factor 1 (IGF-1) on transplanted bone marrow mesenchymal stem cells (BMSCs), for treatment of acute myocardial ischaemia.
  
  
  METHODS
  After ligation of the left anterior descending artery, rabbits were divided into a Control group, a Factors group (HGF+IGF-1), a BMSC group and a Factors+BMSCs group. Allogenous BMSCs (1 × 10(7)) and/or control-released microspheres of 2 μg HGF+2 μg IGF-1 were intramyocardially injected into infarcted regions. Apoptosis and differentiation of implanted BMSCs, histological and morphological results, and cardiac remodelling and function were evaluated at different time points. In vitro, BMSCs were exposed to HGF, IGF-1 and both (50 ng/ml) and subsequently proliferation, migration, myocardial differentiation and apoptosis induced by hypoxia, were analysed.
  
  
  RESULTS
  Four weeks post-operatively, the above indices were significantly improved in Factors+BMSCs group compared to the others (P < 0.01), although Factors and BMSCs group also showed better results than Control group (P < 0.05). In vitro, HGF promoted BMSC migration and differentiation into cardiomyocytes, but inhibited proliferation (P < 0.05), while IGF-1 increased proliferation and migration, and inhibited apoptosis induced by hypoxia (P < 0.05), but did not induce myocardial differentiation. Combination of HGF and IGF-1 significantly promoted BMSCs capacity for migration, differentiation and lack of apoptosis (P < 0.05).
  
  
  CONCLUSIONS
  Combination of HGF and IGF-1 activated BMSCs complementarily, and controlled release of the two factors promoted protective potential of transplanted BMSCs to repair infarcted myocardium. This suggests a new strategy for cell therapies to overcome acute ischemic myocardial injury.
authors.affiliation: Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Guang-Wei
authors.initials: GW
authors.lastname: Zhang
authors.affiliation: Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang, 110001, China.|The Cardiovascular Research Center of China Medical University, Shenyang, 110001, China.
authors.forename: Tian-Xiang
authors.initials: TX
authors.lastname: Gu
authors.affiliation: Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Guan
authors.affiliation: Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, 110001, China.|Department of Anesthesiology of the First Affiliated Hospital of Dalian Medical University, Dalian, 116000, China.
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Sun
authors.affiliation: Department of Radiology, The First Hospital of China Medical University, Shenyang, 110001, China.|Key Laboratory of Diagnostic Imaging and Interventional Radiology of Liaoning Province, The First Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Qi
authors.affiliation: Department of Cardiology, The First Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Xue-Yuan
authors.initials: XY
authors.lastname: Li
authors.affiliation: Department of Echocardiography, The First Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Wang
authors.affiliation: Institute of Biomedical Engineering, Peking Union Medical College, Beijing, 100010, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Lv
authors.affiliation: Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Da-Qing
authors.initials: DQ
authors.lastname: Jiang
authors.affiliation: Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000601:surgery; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D017228:Hepatocyte Growth Factor / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009203:Myocardial Infarction / Q000188:drug therapy*; D032383:Myocytes, Cardiac / Q000166:cytology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011817:Rabbits
chemical_list: D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I