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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* o* C: c/ x0 y' 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 ,8 n5 q8 b3 A9 h( S) f
裴雪涛1 , 31 E- K! C& y0 Z5 Q* J8 Y0 S
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,1 V, ~+ N$ ^1 I5 c/ U
陕西省杨凌712100
9 t8 n( y" `8 D2 X9 \% s* X2 Q* ~7 z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,5 r( _7 h8 l: 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, f9 f3 Y8 T. Y2 J4 f) {9 U
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
- G" g0 f: ?' ]( ]0 s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$ w7 k: C) O( c1 {5 A6 M9 s% H
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
3 e/ M0 s" G5 J! ]" 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
) W( B  l: ~  q# e, q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+ w" N6 u6 F( o
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 ±
  v3 ^. u. q$ r% e# E8 y2109 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
9 e" h% C/ O! T( _& m+ k! ^& K, OPD 的种子细胞。3 @" P6 U, A; i) g6 f9 y* e# M% I
关键词: 骨髓间充质干细胞; 大鼠; 脑; 分化; 迁移8 z2 [% F5 Q, A
中图分类号: Q2542 F  w) U# W$ @) g" F
Migration and differentiation of human bone marrow mesenchymal stem; c( z! {5 o8 V& a7 ?2 t
cells in the rat brain
5 [$ N: a% r4 lHOU Ling2Ling1 , ZHENGMin1 , WANG Dong2Mei1 , YUAN Hong2Feng1 , LI Hai2Min1 , CHEN Lin1 ,
3 T& T% R; b0 s3 m( j( cBAI Ci2Xian1 , ZHAN G Yong2 , PEI Xue2Tao1 , 3
9 W1 _8 ~3 Z% T  s1Beijing Instit ute of Transf usion Medicine , Beijing 100850 ; 2 Northwest Sci2Tech University of A gri2
; k' U5 A- j2 m8 s' W+ k1 T5 N$ U; l! O4 [: Gcul t ure and Forest ry , Yangling , S hanxi 712100
2 d+ |5 K" R5 o4 v& VAbstract : 　Bone marrow mesenchymal stem cells (MSCs) are multipotent tissue stem cells that can be induced
$ Y: u& @2 Y( d- j( J* Tin vit ro to differentiate into a variety of cells such as osteoblasts , chondrocytes and adipocytes. MSCs are useful, ^3 _& x5 @% d- n* J
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! V. w0 R& R1 n* N7 s9 F8 kvehicles for both cell and gene therapy for a variety of diseases. Here , we injected human MSCs with enhanced( m8 e3 n* }$ }. v: L
green fluorescent protein (EGFP) into the striatum of Parkinson disease (PD) rat and examined their survival ,* X7 B1 b( y4 I$ v
migration , differentiation , and the behavior changes in PD rats , which will provide a theoretical foundation and  s+ Q- p! ]) }
technical method for clinic PD therapy by stem cells. The results showed that human bone marrow MSCs can  L8 V3 \' {: r) u- b# s
survive in rat brain for a long time (exceeding 70 d) . MSCs were found in multiple areas of the rat brain includ2- X; w. y# ]  E3 \+ _: a+ F
ing the striatum , the corpus callosum , contralateral cortex and even the brain vascular wall. Immunocytochemical# h! q6 ?; N5 \5 E; G2 y+ I6 W- f
staining suggested that implanted cells expressed human neurofilament (NF) , neuron2specific enolase (NSE) and; m7 k5 [1 s" E9 |
glial fibrillary acid protein (GFAP) . At the same time , remission in abnormal behavior of the PD rats appeared.
2 l. f( c6 G1 S7 P$ i5 N& {* QRotation scores decreased gradually from 8186 ±2109 r/ min pre2transplantation to 4187 ±2106 r/ min 90 d post2
: ^# \9 @( e1 N+ Q" wtransplantation (statistic result showed P < 0105)
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