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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" c- z! Z$ N& ^$ [% z5 s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 ,5 L; z0 R+ Q0 b
裴雪涛1 , 3
1 }2 D5 E6 L" {* i4 `2 ]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 p& o! J2 v1 r" ?1 s陕西省杨凌712100
! z! L9 T( ?! b% m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,
2 Y7 q9 q5 K* @9 F$ M* Z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% H, X; p+ X6 n0 y2 S
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
' Z: ]( c9 Q4 i) a2 U, h; O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 i+ h; b/ \: q
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
" a6 w, c8 |" F4 }$ u2 o: 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
9 f( A7 ?! b/ }+ E' ~& k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
4 ?9 X6 l. k" d" Qlase , 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 ±, N" I" p1 E3 K) C4 n! b- R: T# R, 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) l% Q8 P3 [/ I& F7 G2 v, j" W
PD 的种子细胞。7 \0 D" s4 f" R7 _
关键词: 骨髓间充质干细胞; 大鼠; 脑; 分化; 迁移7 ]! o( J) w& k9 O4 O( _! _
中图分类号: Q254
0 U1 P- d6 J& C9 z  ^Migration and differentiation of human bone marrow mesenchymal stem
( {  @- h+ z6 W% X3 pcells in the rat brain: w' z: F* Z* t$ v- L* W; \
HOU Ling2Ling1 , ZHENGMin1 , WANG Dong2Mei1 , YUAN Hong2Feng1 , LI Hai2Min1 , CHEN Lin1 ,5 f$ n! [9 Z$ p( l
BAI Ci2Xian1 , ZHAN G Yong2 , PEI Xue2Tao1 , 3
9 S& a9 ^! ?( I5 U1Beijing Instit ute of Transf usion Medicine , Beijing 100850 ; 2 Northwest Sci2Tech University of A gri2
  n  j! F& V8 J# Z8 T8 wcul t ure and Forest ry , Yangling , S hanxi 7121004 m1 q* S0 {8 s9 C: n6 A1 r9 p
Abstract : 　Bone marrow mesenchymal stem cells (MSCs) are multipotent tissue stem cells that can be induced6 Q2 \  m) r/ _) h( X% @# r
in vit ro to differentiate into a variety of cells such as osteoblasts , chondrocytes and adipocytes. MSCs are useful
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( Q. q. M: S$ s6 p" A! K+ z" ^( Lvehicles for both cell and gene therapy for a variety of diseases. Here , we injected human MSCs with enhanced
3 C- \/ \) J8 l. Jgreen fluorescent protein (EGFP) into the striatum of Parkinson disease (PD) rat and examined their survival ,$ o* q- u2 v8 F4 e! X  e2 I
migration , differentiation , and the behavior changes in PD rats , which will provide a theoretical foundation and# m; _- g4 L# I0 E1 i: P. `& r, A
technical method for clinic PD therapy by stem cells. The results showed that human bone marrow MSCs can
1 @* N6 Q" c/ g" z# o1 isurvive in rat brain for a long time (exceeding 70 d) . MSCs were found in multiple areas of the rat brain includ2( X$ p8 d) G1 M% B. l; V
ing the striatum , the corpus callosum , contralateral cortex and even the brain vascular wall. Immunocytochemical
; W1 H. L! f1 L5 fstaining suggested that implanted cells expressed human neurofilament (NF) , neuron2specific enolase (NSE) and
' P( v9 j5 O$ E! G" kglial fibrillary acid protein (GFAP) . At the same time , remission in abnormal behavior of the PD rats appeared.! @8 g% }% B) N: T" |" Q7 u, O0 r
Rotation scores decreased gradually from 8186 ±2109 r/ min pre2transplantation to 4187 ±2106 r/ min 90 d post2
& M; D; M, h( _+ ^8 r8 Dtransplantation (statistic result showed P < 0105): A# ?3 F% w3 q9 S& C$ @# Q
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