血管内皮生长因子基因转染骨髓间充质干细胞同种异体移植治疗大鼠急性心肌梗死

目的探讨同种异体血管内皮生长因子(VEGF)基因转染的骨髓间充质干细胞(MSCs)在大鼠梗死心脏局部存活、分化及对心功能的影响;明确同种异体干细胞及VEGF基因转染干细胞移植治疗急性心肌梗死(AMI)的可行性及效果。方法雄性SD大鼠30只,随机分为单纯注射培养基对照组、MSCs治疗组及VEGF基因转染MSCs治疗组。分离纯化雄性Wistar大鼠骨髓间充质干细胞(rMSCs),于左冠状动脉前降支结扎1h后植入到SD大鼠心组织,移植4周后检测心功能并取心脏行组织染色检查。结果异体大鼠MSCs可在梗死心组织定居、生存;免疫组化检测MSCs转化为心肌细胞及血管内皮细胞;与对照组比较VEGF基因转染异体细胞移植组左室射血分数升高(P<0.05),梗死边缘区心肌面毛细血管数目明显增加(P<0.05)。结论同种异体VEGF基因转染MSCs移植治疗AMI可行、有效。

Transplantation of exogamous mesenchymal stem cells with transferred vascularendothelial growth factor gene applied for treatment of acute myocardial infarction in rat

Objective To investigate the possibility of survival,migration and differentiation of rat mesenchymal stem cells(rMSCs) in host myocardium , the effects of rMSCs and exogenous rMSCs which were transferred with adenovirus mediated vascular endothelial growth factor 165 gene (AdVEGF_ 165) in transplantation for the recovery of the function of heart with myocardial infarction; To observe the feasibility of using exogenous adult stem cells for cell therapy. Methods rMSCs were cultured in vitro and transferred by AdVEGF_ 165, ELISA method was applied to assay the expression and secretion of VEGF;30 male SD rats were randomly divided into three groups: acute myocardial infarction control group (control,n=10),myocardial infarction plus cell transplantation group (AMI+Cell,n=10) and myocardial infarction plus VEGF-transfer-cell transplantation group(A MI+VEGF-Cell,n=10).The infracted hearts were induced by occlusion of left coronary artery. Male Wistar rats MSCs were isolated and purified. Then the cells were implanted into the infracted hearts of male SD rats. Heart functions were measured by ultrasound 4 weeks after implantation. The hearts were harvested 4 weeks after implantation for immunohischemistry. Results ELISA show: upper liquid of transfer group has agreat deal of VEGF expression and more significant than control group(P<0.05); Immunohistochemistry show: Purified rMSCs survived and homed in exogenous host hearts; ultrasound show: improvement degree of EF of VEGF-transfer-cell transplantation group more significant than other groups(P<0.05).Conclusion The purified rMSCs can survive in exogenous host hearts without addition of any immunosuppressant. rMSCs which were transferred AdVEGF_ 165 take part in myocardium regeneration and have beneficial effects on heart function.