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Transplantation of bcl-2 gene-modified bone marrow mesenchymal stem cells improves cardiac function and angiogenesis in rabbit ischemic car-diac insufficiency model
Authors:GAO Qing  LI Shu-ren  XUN Li-ying  YUAN Ke-xin  XIE Yue-tao  ZHANG Qian-hui  HAO Qing-qing  DANG Yi  QI Xiao-yong
Affiliation:1. Graduate School of Hebei Medical University, Shijiazhuang 050051, China;2. Department of Cardiology, Hebei General Hospital, Shijiazhuang 050051, China
Abstract:AIM: To investigate the effects of transplantation of bone marrow mesenchymal stem cells (BMSCs) modified by bcl-2 gene on myocardial cell apoptosis, angiogenesis and cardiac function in the rabbit after acute myocardial infarction (MI).METHODS: The rabbit BMSCs were isolated, cultured and purified in vitro. The BMSCs were transfected with adenovirus or adenovirus-Bcl-2. The rabbit model of MI was established by ligation of left anterior descending branch. The rabbits were injected with Ad-Bcl-2-BMSCs (MI+Bcl-2-BMSCs group), Ad-BMSCs (MI+BMSCs group) and DMEM (MI group) in infarction marginal zone 2 weeks after ligation. The cardiac function was evaluated by echocardiography.The apoptosis of myocardial cells was measured by TUNEL. The mRNA expression of VEGF was detected by real-time PCR. The expression of CD31 was examined by immunohistochemical staining, and new blood capillaries were counted at 4 weeks after BMSCs transplantation. The correlation of the above values with cardiac function was analyzed.RESULTS: The cardiac function was better, the apoptotic rate was lower, the mRNA expression of VEGF and the capillary density were higher in both MI+Bcl-2-BMSCs group and the MI+BMSCs group than those in MI group, and those in MI+Bcl-2-BMSCs group increased more obviously.The left ventricular ejection fraction (LVEF) had a negative correlation with the myocardial cell apoptosis rate. A positive correlation with the mRNA expression level of VEGF and the capillary density was also observed.CONCLUSION: The transplantation of BMSCs modified by bcl-2 gene significantly reduces the myocardial cell apoptosis, promotes angiogenesis, improves heart function of the rabbits with MI.
Keywords:Bone marrow mesenchymal stem cells  Gene therapy  Myocardial infarction  bcl-2 gene  
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