中国组织工程研究

中国组织工程研究 ›› 0, Vol. ›› Issue (0): 70-75.doi: 10.3969/j.issn.1673-8225.2012.01.015

• 骨髓干细胞 • 上一篇    下一篇

人骨髓间充质干细胞移植促进脑梗死大鼠神经细胞再生和神经功能恢复

柳太云1，熊  符2，林  军1，王传森1，张  成3
  

  1. 1 贵州省人民医院神经内科，贵州省贵阳市 550002；
    2 南方医科大学生理教研室，广东省广州市 510515；
    3 中山大学第一附属医院神经内科，广东省广州市 510080；
  • 收稿日期:2011-11-04 修回日期:2011-12-07
  • 通讯作者: 柳太云☆，男，1964 年生，贵州省印江县人，汉族，博士，主任医师，2005 年于中山大学毕业，主要从事神经心理神经遗传及干细胞移植的研究。贵州省人民医院神经内科，贵州省贵阳市 550002 taiyunliu@163.com
  • 作者简介: 柳太云☆，男，1964年生，贵州省印江县人，汉族，博士，主任医师，2005年于中山大学毕业，主要从事神经心理、神经遗传及干细胞移植的研究。贵州省人民医院神经内科，贵州省贵阳市 550002

Human bone marrow mesenchymal stem cells transplantation induces neural regeneration andimproves the recovery of nerve function in a rat stroke model

Liu Tai-yun1, Xiong Fu2, Lin Jun1, Wang Chuan-Sen1, Zhang Cheng3    

  1. 1Department ofNeurology, GuizhouProvincial Hospital,Guiyang 550002,Guizhou Province,China;
    2Insititute ofPhysiology, SouthernMedical University,Guangzhou510515, GuangdongProvince, China;
    3Department ofNeurology, the FirstAffiliated Hospital ofSun Yat-senUniversity,Guangzhou510080, China;
  • Received:2011-11-04 Revised:2011-12-07
  • Contact: Liu Tai-yun,Department ofNeurology, GuizhouProvincial Hospital,Guiyang 550002,Guizhou Province,China taiyunliu@163.com
  • About author:Liu Tai-yun☆, Doctor, Chief physician, Department of Neurology, Guizhou Provincial Hospital, Guiyang 550002, Guizhou Province, China

PDF

436

被引次数

8

摘要：

背景：有研究表明，骨髓间充质干细胞或神经干细胞同种移植可改善脑梗死模型鼠神经功能。
目的：观察人骨髓间充质干细胞在移植大鼠脑神经功能梗死局部的内存活、迁移情况及神经细胞再生。
方法：将人骨髓间充质干细胞经静脉注入免疫抑制的大脑中动脉闭塞模型大鼠，每周观察、记录移植大鼠的行为和神经功能状况(NSS评分、转棒实验)；于移植后1~8周处死大鼠，采用免疫组织化学染色，免疫荧光染色和RT-PCR检测检测移植大鼠大脑人细胞核抗原、神经干细胞标志物(巢蛋白)及神经细胞标志物(神经元核心抗原、脑型微管蛋白、胶质纤维酸性蛋白)的表达。
结果与结论：骨髓间充质干细胞移植后2周，脑梗死模型鼠NSS评分明显降低(P < 0.05)、转棒实验停留时间明显延长(P < 0.01)，神经功能得到改善(P < 0.05)。人骨髓间充质干细胞移植后1~8周，在移植大鼠病变侧室管膜下区、海马齿状回、梗死灶周围均可检测到人细胞核抗原阳性细胞。移植后一二周，在移植大鼠病变侧室管膜下区、海马齿状回(CA1, CA3区)、梗死灶周围可见部分巢蛋白阳性细胞和mRNA表达，存续至8周。移植后2周，在移植大鼠病变侧室管膜下区、海马齿状回、梗死灶周围可见部分神经元核心抗原、脑型微管蛋白阳性细胞和mRNA的表达。移植后4~8周，在海马、梗死灶周围可见少量胶质纤维酸性蛋白阳性细胞和少量mRNA的表达。结果证实，静脉移植人骨髓间充质干细胞能在脑梗死模型大鼠脑内存活、并迁移至病变部位，继而分化为神经细胞，促进新生神经细胞的形成，改善移植大鼠的神经功能。

关键词: 脑梗死, 骨髓间充质干细胞, 神经细胞再生, 分化, 干细胞移植

Abstract:

BACKGROUND: Studies have shown that allograft of bone marrow mesenchymal stem cells (BMSCs) or neural stem cells (NSCs) can improve the nerve function of rat stroke model.  
OBJECTIVE: To investigate survival and migration of BMSCs in part of the infarction region of transplanted rat and the neural regeneration. 
METHODS: Human BMSCs were transplanted into an immunosuppressed rat model of focal cerebral ischemia by vein. Behavioral recovery (neurological severity scores, NSS; rotarod test) and nerve function were also observed once a week. The rat were euthanized at 1-8 weeks after transplantation, and the expression of human nuclear antigen (HNA), marker of neural stem cells (Nestin) and nerve cell markers (Neuronal nuclei, cerebral tubulin, glial fibrillary acidic protein) were analyzed by immunohistochemistry staining, immunofluorescence staining and RT-PCR. 
RESULTS AND CONCLUSION: At 2 weeks after BMSCs transplantation, the NSS score of rat stroke model was decreased significantly (P < 0.05), and the residence time of the rotarod test was significantly prolonged. At 1-8 weeks after BMSCs transplantation, HNA+ cells were identified in subependymal region, hippocampus dentate gyrus and the site around the infarction. At 1 and 2 weeks after BMSCs transplantation, Nestin positive cells and mRNA expression could be seen in subependymal region, hippocampus dentate gyrus (CA1, CA3) and the site around the infarction, and lasted for 8 weeks. Two weeks later, HNA, cerebral tubulin positive cells and mRNA expression could be seen in subependymal region, hippocampus dentate gyrus and the site around the infarction. At 4-8 weeks after BMSCs transplantation, a small amount of glial fibrillary acidic protein positive cells and mRNA expression could be seen in subependymal region, hippocampus dentate gyrus and the site around the infarction. The data indicate that human BMSCs can survive and migrate to focal cerebral ischemia of a rat stroke model by intravenous delivery, then differentiate into nerve cells, promote the formation of nerve cells and improve the recovery of neurological function.

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