同种异体骨髓间充质干细胞在大鼠心脏的迁移及分化  

Migration and differentiation of exogenous rat mesenchymal stem cells engrafted into normal and injured hearts of rats

作　　者：牛丽丽[1] 郑敏[1] 曹丰[1] 谢超[1] 李海民[1] 岳文[1] 高艳红[1] 白慈贤[1] 祝善俊[2] 裴雪涛[1] 

机构地区：[1]北京军事医学科学院输血研究所干细胞研究室,现在北京军区总医院心内科100850 [2]重庆第三军医大学新桥医院心内科

出　　处：《中华医学杂志》2004年第1期38-42,共5页National Medical Journal of China

基　　金：国家 973计划资助项目 (CB5 0 990 6);国家 863计划重大专项资助项目 (AA2 0 5 0 5 1);北京市科委重大项目 ( 2 0 0 2 4 89)基金资助

摘　　要：目的　探讨同种异体骨髓间充质干细胞 (MSC)在大鼠心脏定居存活情况、同种异体移植是否可行。正常心脏微环境与梗死心脏微环境对骨髓间充质干细胞 (MSC)迁移、分化的影响。方法　雌性Wistar大鼠 35只 ,①正常心脏MSC移植组 (1 0只 ) ;②急性心肌梗死对照组 (AMI,1 0只 ) ;③心肌梗死MSC移植组 (1 0只 ) ;④单个核细胞治疗组 (5只 )。结扎左冠状动脉前降支造成心肌梗死模型。分离纯化来自雄性Wistar大鼠的骨髓MSC ,于冠脉结扎后 1～ 3h植入到雌性正常大鼠和心肌梗死大鼠心脏组织 ,模拟同种异体细胞移植治疗。于细胞移植后 1 0周取心脏检测各种指标。结果(1 )经纯化的大鼠MSC在同种异体大鼠心脏可定居、生存 ,而未经纯化的单个核细胞移植在同种异体大鼠心脏未见存活 ;(2 )在正常心脏微环境中 ,带蓝色荧光的供体MSC细胞核呈小岛屿状分布 ,与宿主心肌纤维排列无关 ;而在心肌梗死模型大鼠心脏微环境中 ,蓝色细胞核分布广泛 ,呈椭圆形 ,似心肌细胞核 ,其排列方向与宿主心肌纤维排列方向一致 ,免疫组化检测胞浆心肌特异蛋白染色阳性。结论　纯化的MSC具有免疫耐受特性 ,无需加用免疫抑制剂 ,可进行同种异体移植 ;同种异体MSC在正常心脏微环境中不发生迁移、分化 ;Objective To investigate the effects of different microcircumstances on the migration and differentiation of grafted rat mesenchymal stem cells (rMSC) in host myocardium and the feasibility of treatment of myocardial infarction by exogenous adult stem cells. Methods rMSC were isolated from the femurs and tibiae of a male Wistar rat and then purified, made into cell suspension, and labeled with DAPI. 35 female Wistar rat were divided randomly into four groups: acute myocardial infarction control group (AMI group, n =10, the descending anterior branch of left coronary artery was ligated), acute myocardial infarction + rMSC transplantation group (AMI+rMSC group, n =10, 1～3 hours after the ligation DAPI labeled rMSC were injected into the peri infarct tissues), normal heart+rMSC transplantation group (normal heart+MSC group, n =10, DAPI labeled rMSC were injected into the corresponding myocardium), and mono nuclear cells transplantation group (AMI+MNCS, n =5 DAPI labeled mononuclear cells were injected into he periinfarct tissues). Ten weeks after the implantation, the rats were killed and their hearts were harvested. Immunohischemistry was used to examine the troponin, GATA 4 and connexin 43. Results No lymphocyte proliferation and immonologic rejection were seen in the cardiac tissues of the rats implanted with rMSC. DAPI labeled rMSC with blue nuclei were distributed extensively in the myocardium of the AMI+rMSC group, ovoid in shape and arranged in parallel with the cardiac muscle fibers, and were distributed sporadically like islands in the myocardium of the normal heart+rMSC group, irregular in shape and not arranged in parallel with the cardiac muscle fibers. No blue nucleus was seen in the cardiac tissues of the hearts implanted with DAPI labeled mononuclear cells. Troponin and GATA4 were positive immunohistochemically in the implanted rMSC with blue nuclei and the host cardiac muscle cells of the AMI group and AMI+rMSC group, however, were negative in the implanted rMSC with blue

关 键 词：同种异体移植 骨髓间充质干细胞 大鼠 心脏迁移 微环境 免疫耐受 

分 类 号：R541[医药卫生—心血管疾病]