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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0 V. e% W7 e0 k& Y+ O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 ,
6 x9 \+ e! a& `裴雪涛1 , 3/ y" j$ K2 A- V: N' `( P
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,
" a; c& E1 t' n1 L) o陕西省杨凌712100
0 P' Q& u9 S$ E0 S2 h% m6 |) _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,
: e' X: F5 ]/ X7 q4 ?, W, F) Q1 s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
" b. z/ U1 u! t3 H+ g5 [! x1 V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
/ R! z# G- x# W2 X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4 a  v# R! I; f% W8 x  b
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2 c, G6 O$ l- }$ J
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# N# P9 ]  w, b) P3 y7 {; E
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 eno2
+ a# S- ?7 D% _$ V; `) Nlase , 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 ±/ h2 w+ ~! [2 R8 X& _2 X% U
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
; ]5 M' g+ g- ~PD 的种子细胞。
2 N2 [6 O% d9 @  u& g) T关键词: 骨髓间充质干细胞; 大鼠; 脑; 分化; 迁移
( x5 F/ [! v* l! c8 `6 L7 ~3 u中图分类号: Q254* ^) _$ f2 j' _3 j  D+ ]  x2 }
Migration and differentiation of human bone marrow mesenchymal stem( P! D* P& P' t
cells in the rat brain! J4 i/ x! Y' N& D' q6 X) R
HOU Ling2Ling1 , ZHENGMin1 , WANG Dong2Mei1 , YUAN Hong2Feng1 , LI Hai2Min1 , CHEN Lin1 ,
  h& B) [1 D; \( @- l7 q* VBAI Ci2Xian1 , ZHAN G Yong2 , PEI Xue2Tao1 , 3' e% X* P4 H5 H8 n4 A8 w2 g& ]7 ~3 E" }
1Beijing Instit ute of Transf usion Medicine , Beijing 100850 ; 2 Northwest Sci2Tech University of A gri2
7 _- ~. n6 V) |. Fcul t ure and Forest ry , Yangling , S hanxi 712100
) m0 b: ^9 H/ k) \4 cAbstract : 　Bone marrow mesenchymal stem cells (MSCs) are multipotent tissue stem cells that can be induced
9 y+ W- v' Y' a# Q6 L, qin vit ro to differentiate into a variety of cells such as osteoblasts , chondrocytes and adipocytes. MSCs are useful
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1 B# D: s7 y, s+ Hvehicles for both cell and gene therapy for a variety of diseases. Here , we injected human MSCs with enhanced( ~+ i- o" _! C6 L  W# a6 m
green fluorescent protein (EGFP) into the striatum of Parkinson disease (PD) rat and examined their survival ,) z4 B* H  a6 e+ t' _
migration , differentiation , and the behavior changes in PD rats , which will provide a theoretical foundation and
3 ]: y6 L- f$ }technical method for clinic PD therapy by stem cells. The results showed that human bone marrow MSCs can- v& ~3 |- v$ K2 U1 A( E, l8 y
survive in rat brain for a long time (exceeding 70 d) . MSCs were found in multiple areas of the rat brain includ2% i) N2 [+ o8 P" k6 W% ?
ing the striatum , the corpus callosum , contralateral cortex and even the brain vascular wall. Immunocytochemical: H' Z( v* c$ A
staining suggested that implanted cells expressed human neurofilament (NF) , neuron2specific enolase (NSE) and% `$ \3 R. s* k- H
glial fibrillary acid protein (GFAP) . At the same time , remission in abnormal behavior of the PD rats appeared.7 y! {' u3 h/ j, s8 i: r
Rotation scores decreased gradually from 8186 ±2109 r/ min pre2transplantation to 4187 ±2106 r/ min 90 d post2
2 {& }1 \: u! {) D# ltransplantation (statistic result showed P < 0105)) m) j* M  H. A3 u- D) I
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