骨髓间充质干细胞诱导心脏成纤维细胞向肌纤维母细胞转化:不同时期心肌梗死区域的最佳微环境

Bone marrow mesenchymal stem cells-induced transformation of cardiac fibroblasts into myofibroblasts:Optimal microenvironment of myocardial infarction at different stages

背景:骨髓间充质干细胞移植能够有效改善心肌梗死后的心功能,其作用机制可能与移植部位大量肌纤维母细胞的聚集有关,但至今仍缺少证据来证实聚集的肌纤维母细胞是由骨髓间充质干细胞还是由成纤维细胞转化而来?目的:观察不同时期心肌梗死微环境对大鼠骨髓间充质干细胞诱导心脏成纤维细胞向肌纤维母细胞转化的影响。方法:将培养组分为3组:大鼠骨髓间充质干细胞、心脏成纤维细胞单培养组,以及两种细胞共培养组,加入心肌梗死后不同时期心肌匀浆干预7～28d,并设立不加心肌匀浆的空白对照组,运用免疫细胞化学染色方法,检测不同干预组间平滑肌肌动蛋白(α-SMA)表达及成纤维细胞转化为肌纤维母细胞数量间的差异。结果与结论:加用心肌梗死第14天梗死周边区域心肌匀浆干预的共培养组,检测到心脏成纤维细胞转化为肌纤维母细胞的阳性率最高。提示心肌梗死后微环境下,骨髓间充质干细胞能诱导诱导心脏成纤维细胞转化为肌纤维母细胞,而心肌梗死后14d的心肌梗死微环境是骨髓间充质干细胞诱导心脏成纤维细胞转化为肌纤维母细胞的最佳微环境。

BACKGROUND：Bone marrow mesenchymal stem cells （BMSCs） can effectively improve heart function following myocardial infarction.Its action mechanism is associated with aggregation of a large number of myofibroblasts in the transplant region, but few reports have verified that gathered myofibroblasts are transformed from BMSCs or from fibroblasts.OBJECTIVE：To explore the impact of microenvironment of myocardial infarction in different periods in rat BMSCs inducing cardiac fibroblasts into myofibroblasts.METHODS：The culture group was assigned to three groups：rat BMSCs group, cardiac fibroblasts group and combination group Myocardial homogenate was added at different times after myocardial infarction for 7-28 days.A blank control group was set, without myocardial homogenate.Immunocytochemical staining was used to determine the differences of α-smooth muscle actin （α-SMA） expression and the number of fibroblasts into myofibroblasts between the two groups.RESULTS AND CONCLUSION：In the combination group, the positive rate of cardiac fibroblasts into myofibroblasts is highest, when BMSCs and cardiac fibroblasts were cultured together and intervened by myocardial homogenate on day 14 after myocardial infarction.Results suggest that in the microenvironment of post-myocardial infarction, BMSCs can induce cardiac fibroblasts into myofibroblasts, while the microenvironment of post-myocardial infarction on day 14 is the best one.