骨髓间充质干细胞对梗死心肌中肌纤维母细胞调控机制的研究

项目名称： 骨髓间充质干细胞对梗死心肌中肌纤维母细胞调控机制的研究

项目编号： No.30871053

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 金属学与金属工艺

项目作者： 周胜华

作者单位： 中南大学

项目金额： 30万元

中文摘要： ①在模拟梗死微环境下, MSCs可以旁分泌高浓度的TGF-β#65292;诱导成纤维细胞向肌纤维母细胞转型; 梗死区的生长因子TGF-β#20063;能诱导MSCs分化为肌纤维母细胞； ②体内移植实验观察到MSCs移植可增加毛细血管新生、减少梗死面积，增加梗死区的胶原I、III合成，减少IL-1β12289;IL-6的表达，增加VEGF的表达，改善梗死部位修复； ③MSCs移植后梗死部位有大量肌纤维母细胞聚集，同时我们发现过表达TGF-β#30340;MSCs移植后可显著增加梗死区的肌纤维母细胞形成；共聚焦显微镜观察发现MSCs组在梗死区域αMA、Vimentin免疫荧光化学染色阳性时，同时可见到DAPI染色，说明MSCs在梗死区可转型分化为肌纤维母细胞； ④过表达miR126的MSCs可通过AKT/ERK途径转化成内皮细胞并形成毛细血管管腔样结构，体内移植过表达MiRNA126可显著提高MSCs在梗死区的存活率，并通过AKT/ERK途径促心肌梗死区血管新生、减少梗死面积； ⑤过表达miR-1-MSCs移植治疗大鼠心梗模型，能促使MSCs向心肌细胞分化, 并显著增加毛细血管新生、减少梗死面积。

中文关键词： 心肌梗死；骨髓间充质干细胞；心室重构；肌纤维母细胞

英文摘要： ①MSCs can paracrine high concentrations of TGF-β which induced fibroblasts transition to myofibroblasts in the analog infracted heart microenvironment. The growth factor-TGF-βcan also induction of MSCs differentiate into myofibroblasts in the infarcted zone of rat hearts. ②Transplantation of MSCs can enhance angiogenesis and reduce infarcted size in myocardial infarction rat model. Moreover, the stem cells improve cardiac repair efficiently due to increasing the expression of collagen I, III and VEGF in the infarcted zone, but decreasing the expression of IL-1βnd IL-6. ③More myofibroblasts were found at infarted zone after transplantation of MSCs overexpressing TGF-βcompared to transplantation of untreated cells. Confocal microscopy revealed that immunofluorescence staining of αMA and Vimentin were positive in some transplanted cells, which nucleus stained with DAPI. This indicating that MSCs can differentiate into myofibroblasts in the infarcted area. ④MSCs modified with miR-126 can differentiate into endothelial-like cells and have the ability of forming blood vessel. Transplantation of the gene-transfected cells can improve angiogenesis and decrease infarct size in rat hearts, which may be due to the growth survival of MSCs and the stimulation of AKT/ERK-related pathway. ⑤Transplantation of MSCs overexpressing miR-1 can decrease infarct size and improve left ventricular function effectively, by promoting the modified cells differentiate toward cardiomyocytes and enhancing angiogenesis in the infarcted area of the rat hearts.

英文关键词： myocardial infarction; MSCs; left ventricular remodeling; myofibroblasts