人骨髓间充质干细胞在成年大鼠脑内的迁移及分化

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侯玲玲1 , 郑　敏1 , 王冬梅1 , 袁红丰1 , 李海民1 , 陈　琳1 , 白慈贤1 , 张　涌2 ,: N, C& W8 C) I1 A0 o- d
裴雪涛1 , 3% r; W* ?" F% c4 h: X+ h
1 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 ; 2西北农林科技大学胚胎工程实验室,8 x$ B( ~/ M& E
陕西省杨凌712100
+ o& @( O7 [( A6 I- B2 T摘　要: 　骨髓间充质干细胞(mesenchymal 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,! p" e0 {7 h$ D* @. u% N$ g& ~
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
2 s2 L3 A1 h  w: E/ I& c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
" P9 d4 ?) n) Q% @& w强型绿色荧光蛋白(enhanced green fluorescent protein , EGFP) 的人骨髓MSCs 注入PD 大鼠脑内纹状体, 观察了人骨髓3 i4 a) j9 T# _* |" d" O7 b6 g
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% V6 o9 w- ^6 r4 P
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
" [) p3 m+ J9 I9 X% g2 O/ H" {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(neuron2specific eno29 P0 o2 ]/ l! @& }
lase , 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8186 ±7 c) {6 [8 O& L0 v
2109 r/ min 下降到4187 ±2106 r/ min , 统计学分析P < 0105 为差异显著。以上观察结果表明, 骨髓MSCs 有望成为治疗
  M! T; M  q# ^: ?PD 的种子细胞。
8 a2 S% P2 C8 ]关键词: 骨髓间充质干细胞; 大鼠; 脑; 分化; 迁移) y7 b# j+ d9 i* U  r1 g* q& S2 Q. b
中图分类号: Q254# Q% b6 v% T, G# }( n
Migration and differentiation of human bone marrow mesenchymal stem# j; |  K2 L, _4 [( G1 Q/ i
cells in the rat brain9 M/ y4 j4 y, H/ s+ {( V, }
HOU Ling2Ling1 , ZHENGMin1 , WANG Dong2Mei1 , YUAN Hong2Feng1 , LI Hai2Min1 , CHEN Lin1 ,
# B  r. q, v& G2 oBAI Ci2Xian1 , ZHAN G Yong2 , PEI Xue2Tao1 , 3
( e! m9 u& Z: _. s( m& ]1 [2 K1Beijing Instit ute of Transf usion Medicine , Beijing 100850 ; 2 Northwest Sci2Tech University of A gri2
, @3 M9 w2 k: U0 q; a- zcul t ure and Forest ry , Yangling , S hanxi 7121001 o- T+ a/ m) ?1 Z9 V) E% {3 r
Abstract : 　Bone marrow mesenchymal stem cells (MSCs) are multipotent tissue stem cells that can be induced
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9 c2 F) x- M" h5 Q9 d* rvehicles for both cell and gene therapy for a variety of diseases. Here , we injected human MSCs with enhanced2 O4 n) j$ v# E2 m1 R5 Q
green fluorescent protein (EGFP) into the striatum of Parkinson disease (PD) rat and examined their survival ,3 r+ D/ b8 r. ]" g) B) A  o
migration , differentiation , and the behavior changes in PD rats , which will provide a theoretical foundation and  b, {  ?/ e: p) ~" V# }
technical method for clinic PD therapy by stem cells. The results showed that human bone marrow MSCs can( |% L4 O6 @% l9 U6 j, q
survive in rat brain for a long time (exceeding 70 d) . MSCs were found in multiple areas of the rat brain includ2# L( D8 h, J! |  o$ p9 u
ing the striatum , the corpus callosum , contralateral cortex and even the brain vascular wall. Immunocytochemical
3 p5 I+ m7 ?# dstaining suggested that implanted cells expressed human neurofilament (NF) , neuron2specific enolase (NSE) and. k0 R# V3 j( p$ p0 D
glial fibrillary acid protein (GFAP) . At the same time , remission in abnormal behavior of the PD rats appeared.7 ]! b; I$ R4 j% V& o" l
Rotation scores decreased gradually from 8186 ±2109 r/ min pre2transplantation to 4187 ±2106 r/ min 90 d post28 R: p. q0 U; }0 n) P
transplantation (statistic result showed P < 0105)- `. i# p& o5 h# h/ I

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