同种异体骨髓间充质干细胞移植治疗大鼠急性心肌梗死

Allogeneic bone marrow mesenchymal stem cell transplantation for acute myocardial infarction in rats

背景:多项研究表明,骨髓间充质干细胞移植可在梗死心肌存活,改善心功能。目的:观察同种异体骨髓间充质干细胞移植治疗大鼠急性心肌梗死后心力衰竭的效果。方法:经Percoll密度梯度离心培养大鼠骨髓间充质干细胞,将39只雌性Wistar大鼠采用结扎左前降支的方法复制急性心肌梗死模型,随机分为DMEM对照组(n=12)、骨髓间充质干细胞治疗组(n=15)和骨髓单个核细胞治疗组(n=12)。8周后行血流动力学、组织病理学及免疫组化等检测。结果与结论:两个治疗组左室舒张末压显著降低,左室内压最大上升和下降速率、左室内压最大下降速率与左室收缩压的比值显著升高;术后体质量显著增加,左室相对质量显著减轻;梗死区Ⅰ、Ⅲ型胶原容积分数显著降低;梗死区血管数目显著增加。两个治疗组之间比较,除骨髓单个核细胞治疗组室间隔厚度减小、梗死边缘区血管数目增加外,其余指标差异均无显著性意义。免疫组化示骨髓间充质干细胞治疗组梗死区内有BrdU阳性细胞,而在骨髓单个核细胞治疗组梗死区内则基本没有BrdU阳性细胞;两个治疗组在心肌梗死区可见较多desmin阳性和cTnT阳性细胞或细胞团存在。结果提示骨髓单个核细胞、骨髓间充质干细胞均能促进梗死区血管新生,降低局部胶原沉积,改善心肌梗死后心室重构,显著改善心脏功能。

BACKGROUND：A number of studies have shown that bone marrow mesenchymal stem cells can survive in the infarcted myocardium and improve cardiac function. OBJECTIVE：To investigate the effects of al ogeneic rat bone marrow mesenchymal stem cells on heart failure in acute myocardial infarction models of rats and possible mechanisms. METHODS：Rat bone marrow mesenchymal stem cells were isolated from the bone marrow of 39 male Wistar rats by density gradient centrifugation with Percol . After ligating anterior descending coronary artery, 39 female Wistar rats were randomly divided into three groups：control group （Dulbecco’s modified Eagle’s medium, n=12）, mesenchyma stem cells group （n=15） and mononuclear cells group （n=12）. Eight weeks later, hemodynamics and left ventricular function were measured. Histopathological and immunohistochemical examinations were performed. RESULTS AND CONCLUSION：Compared with the control group, left ventricular end diastolic pressure, left ventricular relative weight, the col agen volume fraction of type I and type III in the infarction zone of the left ventricle were al significantly decreased, in contrast to ＆#177;dp/dtmax,-dp/dtmax/left ventricular systolic pressure, body weight and vascular density in infarction zone were al significantly increased both in mesenchymal stem cells group and mononuclear cells group. There were no significant differences between two treatment groups except for interventricular septal thickness and vascular density in non-infarction zone. 5-Bromo-2＇-deoxyuridine positive cells were observed in the infarction area of mesenchyma stem cells group but no positive cells in mononuclear cells group. Some bal-like cellmasses were found positively stained with desmin and cardiac troponin T. Results have suggested that embedded bone marrow mesenchymal stem cells survived in exogenous host hearts. The therapy of mononuclear cells and mesenchymal stem cells could limit the left ventricular remodeling after acute myocardial infarction and improve left ventricular function through angiogenesis inducing and col agen deposition decreasing.