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人骨髓间充质干细胞在成年大鼠脑内的迁移及分化

Migration and differentiation of human bone marrow mesenchymal stem cells in the rat brain

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【作者】 侯玲玲郑敏王冬梅袁红丰李海民陈琳白慈贤张涌裴雪涛

【Author】 HOU Ling-Ling 1, ZHENG Min 1, WANG Dong-Mei 1, YUAN Hong-Feng 1, LI Hai-Min 1, CHEN Lin 1, BAI Ci-Xian 1, ZHANG Yong 2, PEI Xue-Tao 1,* 1Beijing Institute of Transfusion Medicine, Beijing 100850; 2Northwest Sci-Tech University of Agriculture and Forestry, Yangling, Shanxi 712100

【机构】 军事医学科学院输血研究所、军事医学科学院干细胞中心西北农林科技大学胚胎工程实验室军事医学科学院输血研究所、军事医学科学院干细胞中心 北京100850北京100850陕西省杨凌712100北京100850

【摘要】 骨髓间充质干细胞 (mesenchymalstemcells,MSCs)是目前备受关注的一类具有多向分化潜能的组织干细胞 ,体外可以分化为骨、软骨、脂肪等多种细胞。因此 ,MSCs是细胞治疗和基因治疗的种子细胞之一。为了探索MSCs的迁移和分化趋势 ,为帕金森病 (Parkinsondisease,PD)的干细胞治疗提供理论和实验依据 ,本实验将体外扩增并转染增强型绿色荧光蛋白 (enhancedgreenfluorescentprotein ,EGFP)的人骨髓MSCs注入PD大鼠脑内纹状体 ,观察了人骨髓MSCs在大鼠脑内的存活、迁移、分化以及注射MSCs前后大鼠的行为变化。结果表明 ,人骨髓MSCs在大鼠脑内可存活较长时间 ( 10周以上 ) ;随着时间的延长 ,MSCs迁移范围扩大 ,分布于纹状体、胼胝体、皮质以及脑内血管壁 ;免疫组化法检测证实MSCs在大鼠脑内表达人神经丝蛋白 (neurofilament,NF)、神经元特异性烯醇化酶 (neuron specificeno lase,NSE)以及胶质原纤维酸性蛋白 ( glialfibrillaryacidprotein ,GFAP) ;PD大鼠的异常行为有所缓解 ,转圈数由 8 86±2 0 9r/min下降到 4 87± 2 0 6r/min ,统计学分析P <0 0 5为差异显著。以上观察结果表明 ,骨髓MSCs有望成为治疗PD的种子细胞

【Abstract】 Bone marrow mesenchymal stem cells (MSCs) are multipotent tissue stem cells that can be induced in vitro to differentiate into a variety of cells such as osteoblasts, chondrocytes and adipocytes. MSCs are useful vehicles for both cell and gene therapy for a variety of diseases. Here, we injected human MSCs with enhanced green fluorescent protein (EGFP) into the striatum of Parkinson disease (PD) rat and examined their survival, migration, differentiation, and the behavior changes in PD rats, which will provide a theoretical foundation and technical method for clinic PD therapy by stem cells. The results showed that human bone marrow MSCs can survive in rat brain for a long time (exceeding 70 d). MSCs were found in multiple areas of the rat brain including the striatum, the corpus callosum, contralateral cortex and even the brain vascular wall. Immunocytochemical staining suggested that implanted cells expressed human neurofilament (NF), neuron-specific enolase (NSE) and glial fibrillary acid protein (GFAP). At the same time, remission in abnormal behavior of the PD rats appeared. Rotation scores decreased gradually from 8 86±2 09 r/min pre-transplantation to 4 87±2 06 r/min 90 d post-transplantation (statistic result showed P<0 05).

【关键词】 骨髓间充质干细胞大鼠分化迁移
【Key words】 mesenchymal stem cellsratbrainmigrationdifferentiation
【基金】 Thisworkwassupportedbythegrantsfrom 863Program ( #2 0 0 2AA2 0 5 0 5 1and #2 0 0 1AA2 1615 1)ofMinistryofScienceandTechnologyofChina,from973Program( #2 0 0 1CB5 0 9906)ofMinistryofScienceandTechnologyofChina,andfromBeijingInnovationProject( #A0 2 0 2
  • 【文献出处】 生理学报 ,Acta Physiological Sinica , 编辑部邮箱 ,2003年02期
  • 【分类号】R329
  • 【被引频次】72
  • 【下载频次】317
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