脂肪间充质干细胞移植改善急性心肌梗死大鼠心功能

Transplantation of adipose-derived mesenchymal stem cell improves cardiac function in rats with acute myocardial infarction

目的探讨自体与异体脂肪间充质干细胞(ADMSC)移植对急性心肌梗死(AMI)大鼠心功能的影响。方法分离BN大鼠和Lewis大鼠ADMSC,将培养的第3代的ADMSC用氯甲基苯并胺二烷基碳花青(CM-DiI)标记。雄性Lewis大鼠45只随机分为对照组、自体细胞移植组(移植自体ADMSC)、异体细胞移植组(移植BN大鼠ADMSC)。结扎大鼠左冠状动脉前降支制备AMI模型,经心内膜将标记后的ADMSC注入大鼠梗死心肌及其周边部位。ADMSC移植后7 d,免疫荧光技术检测CD4^+ T淋巴细胞、 CD8^+ T淋巴细胞和CD68^+巨噬细胞浸润情况; ADMSC移植后7、 14、 28 d,比较移植细胞存活率;细胞移植后28 d,超声心动图检测大鼠心功能,免疫荧光技术检测α平滑肌肌动蛋白(α-SMA)表达观察移植细胞附近血管生成情况。结果经CM-DiI标记的细胞阳性率近100%;细胞移植后7 d,异体细胞移植组移植细胞周围可见淋巴细胞浸润和巨噬细胞增多,自体细胞移植组未见淋巴细胞浸润和巨噬细胞增加;与异体细胞移植组相比,自体细胞移植组细胞移植后7、 14、 28 d,移植细胞存活率明显增加,左心室短轴缩短率(LVFS)以及舒张期左心室前壁厚度(LVAWTd)增加,梗死心肌周边血管生成数量要明显增多。结论自体ADMSC移植对AMI大鼠心功能改善作用明显优于异体ADMSC移植。

Objective To investigate the effects of the transplantation of autologous and allogeneic adipose-derived mesenchymal stem cells(ADMSCs)on the cardiac function in rats with acute myocardial infarction(AMI).Methods Firstly,ADMSCs were isolated from BN and Lewis rats,and the third generation were labeled with CM-DiI.Then 45 male Lewis rats were randomly divided into 3 groups(control group,autologous cell transplantation group,and allogeneic cell transplantation group).The AMI model was established by ligating the rats’left anterior descending artery,and then the infarcted myocardium as well as the peripheral parts was injected by the labeled ADMSCs via the endocardium.At 7 days after ADMSC transplantation,the infiltration of CD4^+T lymphocytes,CD8^+T lymphocytes and CD68^+macrophages were detected by immunofluorescence technique.At 7,14 and 28 days after transplantation,survival rate of the transplanted cells was compared.Then echocardiography was used to detect the rats’cardiac function at 28 days after transplantation.And the expression ofα-smooth muscle actin(α-SMA)was detected by immunofluorescence technique for determining the angiogenesis near the transplanted cells.Results The positive rate of the cells labeled with CM-DiI was nearly 100%.At 7 days after transplantation,lymphocyte infiltration and macrophages were observed around the transplanted cells in the allogeneic cell transplantation group.No lymphocyte infiltration and macrophages were observed in the autologous cell transplantation group.Compared with allogeneic cell transplantation,the survival rate of the transplanted cells increased significantly.Moreover,the left ventricular short axis shortening rate(LVFS)and the diastolic left ventricular anterior wall thickness(LVAWTd)increased at 7,14 and 28 days after transplantation.Meanwhile,the number of angiogenesis around the infarcted myocardium also significantly increased.Conclusion Autologous ADMSC transplantation is significantly better at improving cardiac function in AMI rats than allogeneic ADMSC transplantation.