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 ,1 j) _0 X5 J: E0 s7 @/ ?
裴雪涛1 , 3
0 s2 z" m$ n: A& z  _1 b* E( ^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,
0 g9 ~( ~6 \% {4 |陕西省杨凌712100
; H+ U* l$ h. H! n# c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,/ }+ ]3 O2 D$ N; C0 ?5 @% Q
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
( m( d0 {; J/ {: g6 o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
: l+ m. u* ~6 K# w- L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
7 G! N* P6 ~  z( q- nMSCs 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1 d! g) ^$ O5 T: _$ g  |
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
! U8 w6 h, N2 `/ p+ f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( D4 ]$ v$ Q6 Z6 y3 k4 l: D
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 ±  t- b" ]" x* A& @( |
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
4 Q. }0 f4 ~. F8 Z. G% ZPD 的种子细胞。8 v, ?9 h' @- S
关键词: 骨髓间充质干细胞; 大鼠; 脑; 分化; 迁移- X: _9 P/ ^% v% ]+ x- _+ r
中图分类号: Q254+ g4 x: A  z& J8 A
Migration and differentiation of human bone marrow mesenchymal stem: m- z5 o) p* J& D
cells in the rat brain
* t6 N7 i4 x6 nHOU Ling2Ling1 , ZHENGMin1 , WANG Dong2Mei1 , YUAN Hong2Feng1 , LI Hai2Min1 , CHEN Lin1 ,: u7 k" r6 S3 L5 f" P! e
BAI Ci2Xian1 , ZHAN G Yong2 , PEI Xue2Tao1 , 3
  j& S8 u, e; a! A1Beijing Instit ute of Transf usion Medicine , Beijing 100850 ; 2 Northwest Sci2Tech University of A gri2
6 ?. H  v& Q4 |$ R3 B/ ecul t ure and Forest ry , Yangling , S hanxi 7121008 S: ^. A9 p! E* A5 @1 F
Abstract : 　Bone marrow mesenchymal stem cells (MSCs) are multipotent tissue stem cells that can be induced/ r* T' y# |  x2 l/ B
in vit ro to differentiate into a variety of cells such as osteoblasts , chondrocytes and adipocytes. MSCs are useful
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, M4 O% g7 M9 X. {+ o; avehicles for both cell and gene therapy for a variety of diseases. Here , we injected human MSCs with enhanced
+ f5 [; o$ k0 x6 mgreen fluorescent protein (EGFP) into the striatum of Parkinson disease (PD) rat and examined their survival ,
4 [/ X$ s4 l+ M% S0 W# V1 O, Z) ~migration , differentiation , and the behavior changes in PD rats , which will provide a theoretical foundation and
' q5 d* u7 ?: j& {6 e' Vtechnical method for clinic PD therapy by stem cells. The results showed that human bone marrow MSCs can* e# \" P# j+ l) X6 I& N9 f4 J
survive in rat brain for a long time (exceeding 70 d) . MSCs were found in multiple areas of the rat brain includ2
& B; w7 y/ I6 d; ming the striatum , the corpus callosum , contralateral cortex and even the brain vascular wall. Immunocytochemical# ]+ o( _6 L0 j% J
staining suggested that implanted cells expressed human neurofilament (NF) , neuron2specific enolase (NSE) and
; ?- Y0 [# T: b. d( |4 {glial fibrillary acid protein (GFAP) . At the same time , remission in abnormal behavior of the PD rats appeared.: r. \& C* G4 T- [! |! b% H
Rotation scores decreased gradually from 8186 ±2109 r/ min pre2transplantation to 4187 ±2106 r/ min 90 d post2
7 r: n& ~6 N1 ]6 b- stransplantation (statistic result showed P < 0105)
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