胚胎干细胞移植到大鼠梗死心脏后的分化研究  

Differentiation of embryonic stem cell transplanted into infareted rat hearts

作　　者：钱伟莉 杨新春 于丽萍 郭雷生 高飞 刘秀兰 

机构地区：[1]首都医科大学附属北京朝阳医院心脏中心,100020

出　　处：《中国心血管杂志》2010年第2期130-133,共4页Chinese Journal of Cardiovascular Medicine

基　　金：国家自然科学基金(90919054);国家自然科学青年基金(30600337)资助项目

摘　　要：目的研究胚胎下细胞在梗死心脏微环境下向心肌细胞、成纤维细胞的分化情况。方法将大鼠分为两组,梗死组为正常大鼠通过结扎左前降支(LAD)制备,对照组为正常大鼠。将4,6-二氨基(DAPI)标记的具有伞能分化能力的鼠胚胎干细胞(mESCs)注射人急性心肌梗死大鼠(18只)或对照绀大鼠(16只)的心脏,观察胚胎干细胞在休内的分化情况。结果 DAPI标记的移植mESCs在对照和梗死心脏均能成活并形成稳定的移植岛,同时在移植区有巨噬细胞浸润。mESCs移植2～4周后,心脏特异性肌钙蛋白T(cTnT)阳性的移植mESCs比例在正常心脏较梗死心脏高(2.67%±0.79%比1.06%±0.52%,P<0.01),但4周后cTnT阳性的DAP1标记细胞在正常和梗死心脏的比例差异无统计学意义(1.17%±0.98%比1.07±1,02%,P>0.05)。mESCs在埘照组和梗死组心脏都能分化为成纤维细胞。结论移植mESCs不仪能仔活,还可分化进入大鼠梗死心肌细胞。但是,梗死心脏的微环境不能选择性促进mESCs分化进入心肌细胞。Objective To investigate whether the infarcted cardiac microenvironment can selectively promote embryonic stem cells differentiation into cardiomyocytes. Methods To assess the cardiac differentiation potential of mouse embryonic stein cells （mESCs） injected into normal （n = 16） or acutely-infarcted rat hearts （n = 18）. Results The transplanted 4, 6-diamidino-2-phenylindole （DAPI）-labeled mESCs were able to survive and form stable intra-cardiac grafts both in normal heart and infarcted heart, along with maerophages found specifically in the engraftment area. Two to four weeks after mESCs transplantation, we found that more DAPI positive mESCs differentiated into cardiomyocytes, marked by cardiac troponin T （cTnT）, more in normal heart than those in infarcted heart （2. 67% ±0. 79% vs. 1.06% ± 0. 52% , P 〈 0. 01 ）. However, the discrepancy between the percentage of DAPI-positive cells that express cTnT in normal heart and that in infarcted hearts was diminished at 4 weeks after injection （ 1.17% -＋0. 98% vs. 1.07% -＋ 1.02% , P 〉 0. 05） , when the transverse striation began to present in the mESCs-derived cardiomyocytes. In addition, mESCs could differentiate into vimentin positive cardiac fibroblasts in normal and infarcted hearts. Conclusions Transplanted mESCs can not only survive, but differentiate into cardiomyoeytes in infarcted rat hearts. However, the infarcted cardiac microenvironment cannot selectively prompt mESCs differentiating into cardiomyocytes.

关 键 词：胚胎干细胞 干细胞移植 心肌梗死 

分 类 号：R542.22[医药卫生—心血管疾病]