经静脉移植骨髓间质干细胞治疗脑梗死

目的 观察经静脉移植骨髓间质干细胞(MSC)治疗脑梗死时神经功能缺损的恢复情况,以及MSC在脑梗死灶的分布、迁移与分化情况.方法 经尾静脉将标记的大鼠骨髓间质干细胞(rMSC)或磷酸缓冲液(PBS)植入脑梗死鼠体内,于不同时程对动物神经功能状况进行评分.应用荧光标记及免疫组织化学方法检测移植细胞在脑内存活、迁移及分化情况,细胞化学染色观察rMSC体外分化情况.结果 与PBS组相比,rMSC组大鼠神经功能改善明显(P＜0.001),在显微镜下可见脑移植细胞在梗死区及其周边区聚集并存活,有部分植入细胞分化表达神经细胞表面标志物,而在体外同时程培养的rMSC未见类似分化表达.结论 rMSC经静脉移植后能够在宿主脑内存活、迁移并分化表达神经细胞表型,有促进脑梗死后神经功能恢复的作用.经静脉路移植可以避免脑组织损伤,同时植入的rMSC能更均匀分布并聚集在脑梗死灶.

Effect of Intravenous Administration of Rat Mesenchymal Stem Cells after Cerebral Ischemia in Rats

Objective To observe the therapeutic effects of intravenous administration of rat mesenchymal stem cells(rMSC) after cerebral ischemia in adult rats, which include the improvement of neurological function, the migration of rMSC to infarct focus, and the differentiation of rMSC. Methods Adult male SD rats were subjected to transient(2 hours) middle cerebral artery occlusion(MCAO). rMSC or phosphate buffered saline(PBS) was injected into tail vein at 24 hour after MCAO. Functional outcome measurements using the modified neurological severity scores(mNSS) were performed at 24 hour post-MCAO, 1 week and 2 weeks post-transplantation respectively. Immunohistochemical staining and immunocytochemistry were used synchronously to identify rMSC and their differentiation markers in the brain sections and the cultured rMSC in vitro. Results There was significant neurological function improvement in rats treated with rMSC groups compared with that of PBS groups(P<0.001). After transplantation, rMSC were survived and localized around the ischemic core and its boundary zone, and a few rMSC expressed Nestin, NF-200 and GFAP, but there were no such expression in rMSC cultured in vitro. Conclusion Intravenous administration of rMSC can promote the neurological functional improvement in rat stroke model. rMSC can survive and localize in the ischemic area of the brain, and a few cells express the phenotypic protein marker of neural cells. The benefit of intravenous administration of rMSC show no brain injury and the better distribution of grafted cells.