Effects of heme oxygenase-1 gene modulated mesenchymal stem cells on vasculogenesis in ischemic swine hearts  

作　　者：JIANG Yi-bo ZHANG Xiao-li TANG Yao-liang MA Gen-shan SHEN Cheng-xing WEI Qin ZHU Qi LIU Nai-feng 

机构地区：[1]Department of Cardiology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, China [2]Division of Cardiovascular Diseases, University of Cincinnati, 231 Albert Sabin Way, ML 0542, Cincinnati, OH 45267-0542, USA

出　　处：《Chinese Medical Journal》2011年第3期401-407,共7页中华医学杂志（英文版）

摘　　要：Background Mesenchymal stem cells （MSCs） transplantation may partially restore heart function in the treatment of acute myocardial infarction （AMI）. The aim of this study was to explore the beneficial effects of MSCs modified with heme xygenase-1 （HO-1） on post-infarct swine hearts to determine whether the induction of therapeutic angiogenesis is modified by the angiogenic cytokines released from the implanted cells.Methods In vitro, MSCs were divided into four groups： （1） non-transfected MSCs （MSCs group）, （2） MSCs transfected with the pcDNA3.1-Lacz plasmid （Lacz-MSCs group）, （3） MSCs transfected with pcDNA3.1-hHO-1 （HO-1-MSCs group）,and （4） MSCs transfected with pcDNA3.1-hHO-1 and pretreatment with an HO inhibitor, tin protoporphyrin （SnPP）（HO-1-MSCs＋SnPP group）. Cells were cultured in an airtight incubation bottle for 24 hours, in which the oxygen concentration was maintained at 〈1%, followed by 12 hours of reoxygenation. After hypoxia/reoxygen treatment, ELISA was used to measure transforming growth factor （TGF-β） and fibroblast growth factor （FGF-2） in the supernatant. In vivo,28 Chinese mini-pigs were randomly allocated to the following treatment groups： （1） control group （saline）, （2）Lacz-MSCs group, （3） HO-1-MSCs group, and （4） HO-1-MSCs ＋ SnPP group. About 1×107 of autologous stem cells or an idertical volume of saline was injected intracoronary into porcine hearts 1 hour after MI. Magnetic resonance imaging （MRI） assay and postmortem analysis were assessed four weeks after stem cell transplantation.Results Post hypoxia/reoxygenation in vitro, TGF-β in the supernatant was significantly increased in the HO-1-MSCs （（874.88±68.23） pg/ml） compared with Lacz-MSCs （（687.81±57.64） pg/ml, P 〈0.001）. FGF-2 was also significantly increased in the HO-1-MSCs （（1106.48±107.06） pg/ml） compared with the Lacz-MSCs （（853.85±74.44） pg/ml, P 〈0.001 ）.In vivo, at four weeks after transplantatiBackground Mesenchymal stem cells （MSCs） transplantation may partially restore heart function in the treatment of acute myocardial infarction （AMI）. The aim of this study was to explore the beneficial effects of MSCs modified with heme xygenase-1 （HO-1） on post-infarct swine hearts to determine whether the induction of therapeutic angiogenesis is modified by the angiogenic cytokines released from the implanted cells.Methods In vitro, MSCs were divided into four groups： （1） non-transfected MSCs （MSCs group）, （2） MSCs transfected with the pcDNA3.1-Lacz plasmid （Lacz-MSCs group）, （3） MSCs transfected with pcDNA3.1-hHO-1 （HO-1-MSCs group）,and （4） MSCs transfected with pcDNA3.1-hHO-1 and pretreatment with an HO inhibitor, tin protoporphyrin （SnPP）（HO-1-MSCs＋SnPP group）. Cells were cultured in an airtight incubation bottle for 24 hours, in which the oxygen concentration was maintained at 〈1%, followed by 12 hours of reoxygenation. After hypoxia/reoxygen treatment, ELISA was used to measure transforming growth factor （TGF-β） and fibroblast growth factor （FGF-2） in the supernatant. In vivo,28 Chinese mini-pigs were randomly allocated to the following treatment groups： （1） control group （saline）, （2）Lacz-MSCs group, （3） HO-1-MSCs group, and （4） HO-1-MSCs ＋ SnPP group. About 1×107 of autologous stem cells or an idertical volume of saline was injected intracoronary into porcine hearts 1 hour after MI. Magnetic resonance imaging （MRI） assay and postmortem analysis were assessed four weeks after stem cell transplantation.Results Post hypoxia/reoxygenation in vitro, TGF-β in the supernatant was significantly increased in the HO-1-MSCs （（874.88±68.23） pg/ml） compared with Lacz-MSCs （（687.81±57.64） pg/ml, P 〈0.001）. FGF-2 was also significantly increased in the HO-1-MSCs （（1106.48±107.06） pg/ml） compared with the Lacz-MSCs （（853.85±74.44） pg/ml, P 〈0.001 ）.In vivo, at four weeks after transplantati

关 键 词：heme oxygenase-1 gene mesenchymal stem cells myocardial ischemia/reperfusion VASCULOGENESIS 

分 类 号：Q516[生物学—生物化学] S852.65[农业科学—基础兽医学]