微环境预处理的骨髓间充质干细胞治疗大鼠心肌梗死  

Efficacy comparison between transplanting microenvironmental induced and non-induced bone marrow mesenchymal stem cells in ischemic rat hearts

作　　者：李晓红[1] 符永恒[1] 刘再毅[2] 张光峰[3] 董光富[3] 林秋雄[1] 余细勇[1] 

机构地区：[1]广东省人民医院医学研究中心广东省心血管病研究所广东省医学科学院,广州510080 [2]广东省人民医院影像医学部,广州510080 [3]广东省人民医院风湿免疫科,广州510080

出　　处：《中华心血管病杂志》2009年第8期680-684,共5页Chinese Journal of Cardiology

基　　金：国家自然科学基金面上项目（30672077,30772142）;广东省自然科学基金（06020831,06020821,8251008004000001）

摘　　要：目的观察骨髓间充质干细胞（BMSC）或经预处理分化的BMSC（induced BMSC，iBMSC）移植能否改善心肌梗死大鼠的心功能。方法雄性sD大鼠32只（250—300g），分为假手术组、磷酸缓冲液（PBS）注射组、BMSC移植组和iBMSC移植组共4组，每组8只。将分离的BMSC与心肌细胞（微环境）共培养2周进行预分化，大鼠心肌梗死模型建立1周后，将BMSC或iBMSC细胞悬液注入梗死区的边缘位置。分别于细胞移植后的第1、2和4周，超声心动图检测各组大鼠心脏的左心室射血分数（LVEF），左心室舒张末期内径（LVIDd），左心室收缩末期内径（LVIDs）及短轴缩短率（FS）。移植后第4周进行组织学观察，心脏组织石蜡包埋切片后采用免疫荧光技术检测移植细胞的示踪标记物及心肌标志蛋白的表达情况。结果iBMSC组LVEF在第4周时是（77．3±2．6）％，与假手术组（81．8±3．6）％比较差异无统计学意义（P〉0．05），而PBS组及BMSC组的LVEF值均低于假手术组（P均〈0．05）。PBS组FS移植前后没明显变化，iBMSC组FS从移植前的（24．1±3．9）％上升到第4周的（45．1±3．1）％。M型超声心电图显示iBMSC治疗组左心室收缩能力较细胞移植前明显改善。免疫荧光分析显示，SPIO标记的移植细胞在体内表达心肌细胞标志蛋白α-辅肌动蛋白和缝隙连接蛋白43。结论经过微环境预处理的BMSC较未处理的干细胞改善心功能效果更好。这一研究为干细胞的改造与细胞移植修复心肌梗死提供了强有力的证据。Objective To compare the efficacy of transplanting bone marrow mesenchymal stem cell （BMSC） or microenvironmental induced BMSC （iBMSC） into the ischemic myocardium of rats with myocardial infarction. Methods iBMSC was defined as BMSC co-cultured with myocardial cells for 2 weeks. The stem cells or equal volume PBS were injected into ischemic border zone 1 wk after experimental infarction. Cardiac performance was evaluated at l, 2, and 4 wk after cell transplantation by echocardiography and analyzed histologically at 4 wk after cell transplantations. Results Compared with PBS group, both BMSC and iBMSC transplantations reduced infarct size. iBMSC enhanced the beneficial effects of BMSC on improving cardiac function （ FS： 28.5% ± 4. 3% in PBS, 29. 0% ± 2.0% in BMSC and 45.1% ±3.1% in iBMSC group at 4 weeks post transplantation, iBMSC group vs. PBS group P 〈0. 05, iBMSC group vs. BMSC group P 〈 0. 05 ）. Immunofluorescence microscopy results revealed co-localization of SPIO-labeled transplanted cells with cardiac markers for cardiomyocytes, indicating regeneration of damaged myocardium. Conclusion Our data suggest that iBMSC implantation is more effective on improving cardiac function than BMSC implantation in this model, iBMSC might serve as a new promising therapeutic cell source for regenerating ischemic myocardium in patients with post-infarction heart failure.

关 键 词：心肌梗死 间质干细胞移植 细胞分化 

分 类 号：R686[医药卫生—骨科学]