经静脉途径移植骨髓间充质干细胞修复梗死心肌的可行性与安全性研究

Intravenous administration of bone marrow mesenchymal stem cells for repairing acute myocardial infarction: feasibility and safety

目的探讨经静脉注射移植同种异体骨髓来源间充质干细胞(MSC)修复损伤心肌是否可行和安全,观察移植MSC在宿主的归巢与组织学分布。方法雄性Wistar大鼠30只,分为正常大鼠MSC移植组,急性心肌梗死MSC移植组,假手术组,每组10只。结扎冠状动脉左前降支,建立大鼠急性心肌梗死模型。体外分离纯化、扩增同种大鼠骨髓MSC,于建立心肌梗死模型24h给各组大鼠经静脉输注4’6’二乙酰基2苯基吲哚(DAPI)标记的MSC,4周后处死、摘取心脏等脏器,行组织病理切片和免疫组织化学染色。结果(1)在急性心肌梗死MSC移植组,梗死区及其周边部位可见到DAPI标记的MSC;(2)在梗死心肌周边区,移植的MSC胞浆心肌特异性蛋白肌钙蛋白I和转录因子4免疫组织化学染色阳性;(3)在各组大鼠其他脏器,移植的MSC主要分布在肺脏、脾脏和肝脏;(4)细胞移植大鼠心肌组织切片未见淋巴细胞增殖,各脏器没有肿瘤形成。结论经静脉移植的MSC可归巢至大鼠梗死心肌部位,并分化为心肌细胞表型,该方法治疗缺血性心脏病安全、可行。

Objective To explore the feasibility and safety of intravenous injection of homologous bone marrow mesenehymal stem cells （MSC） for repairing injured myocardium and to observe homing and distribution of MSC in host. Methods Myocardial infarction was created by occluding the left anterior desending branch of coronary artery in Wistar rats.24 h after coronary artery occlusion,2 × 10^6/0.1 ml rMSCs labeled with 4＇ ,6＇ -diacetyl-2-phenylindole（DAPI） or 0.1 ml of culture medium as control were injected into the border zone of infarcted region. Four weeks after cell transplantation, the rats were sacrificed and histologie and immunohistochemical characteristics of the hearts were studied. Results Four weeks after transplantation, many DAPI-positive cells could be found in infarction and surrounding areas of the hearts. Immunohistochemieal stainning revealed that the engrafted stem cells expressed both cTnI and desmin. There was no tumor growth in organs of cell-transplanted rats and no lymphocytes proliferation in myocardium sections. Conclusion Exogenous MSCs can play a beneficial role in repairing chronic myocardial infarction.