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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

侯玲玲, 郑敏, 王冬梅, 袁红丰, 李海民, 陈琳, 白慈贤, 张涌, 裴雪涛

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 ；西北农林科技大学胚胎工程实验室，陕西省杨凌712100

摘要

骨髓间充质干细胞(mesenchy mal stem cells , 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MS Cs的迁移和分化趋势，为帕金森病(Parkinson disease , 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(enhanced green fluorescent protein , EGFP)的人骨髓MS Cs注入PD大鼠脑内纹状体，观察了人骨髓MS Cs在大鼠脑内的存活、迁移、分化以及注射MS Cs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、脐眠体、皮质以及脑内血管壁;免疫
组化法检测证实MS。在大鼠脑内表达人神经丝蛋白(neurofilament , N助、神经元特异性烯醇化酶(neurorrspecific enolase, NSE)以及胶质原纤维酸性蛋白(glial fibrillary acid protein, GFAP);PD大鼠的异常行为有所缓解，转圈数由8.86士2. 09 r/ min下降到4.87士2. 06 r/ min，统计学分析P<0.05为差异显著。以上观察结果表明，骨髓MS Cs有望成为治疗PD的种子细胞。

关键词： 骨髓间充质干细胞; 大鼠; 脑; 分化; 迁移

1Vfigration and differentiation of human bone marrow mesenchymal stem cells in the rat brain

HOU Ling Ling, ZHENG Mi, WANG Dong Mei, YUAN Hong Feng, LI Hai- Ming, CHEN Ling, BAI Ci Xian, ZHANG Yong, PEI Xue- Tao

Beijing Institute of Transfusion Medicine, Beijing 100850 ； Northwest Sci-Tech University of Agri-culture and Forestry，Yangling，Shanxi 712100

Abstract

Bone marrow mesenchy mal 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·He re，we injected human MSCs with enhanced green fluorescent protein(EGFP) into the striatum of Parkinson disease(P功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 ste m 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·I m munocytoche micalstaining suggested that implanted cells expressed human neurofilament(NF)，neuron- specific enolase(NSE) and filial fibrillary acid protein(GF AP).At the sa me time，remission in abnormal behavior of the PD rats appeared.
Rotation scores decreased gradually from 8. 86士2. 09 r/ min preransplantation to 4. 87士2. 06 r/ min 90 d post transplantation(statistic result showed P<0.05).

Key words: mesenchy mal stem cells;Rat;Brain;migration;differentiation

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引用本文：

侯玲玲, 郑敏, 王冬梅, 袁红丰, 李海民, 陈琳, 白慈贤, 张涌, 裴雪涛. 人骨髓间充质干细胞在成年大鼠脑内的迁移及分化[J]. 生理学报 2003; 55 (2): .

HOU Ling Ling, ZHENG Mi, WANG Dong Mei, YUAN Hong Feng, LI Hai- Ming, CHEN Ling, BAI Ci Xian, ZHANG Yong, PEI Xue- Tao. 1Vfigration and differentiation of human bone marrow mesenchymal stem cells in the rat brain. Acta Physiol Sin 2003; 55 (2): (in Chinese with English abstract).