骨髓间充质干细胞在大鼠体内的迁移研究  

Engraftment and Migration of Human Messenchymal stem Cells Implanted in the Brains of Rats

作　　者：鲁玲玲[1] 刘玉军[1] 孙晓红[1] 刘华松[2] 孙正[2] 杨慧[1] 

机构地区：[1]首都医科大学北京神经科学研究所 [2]首都医科大学北京口腔医院,北京100054

出　　处：《中国生物工程杂志》2005年第4期22-28,共7页China Biotechnology

基　　金：国家"863"计划资助项目(2003AA326010)北京自然基金重点项目B类北京市教委重点项目(KZ200310025009)

摘　　要：目的:将体外预先标记的骨髓间充质干细胞(mesenchymal stem cells,MSCs)移植到大鼠脑 内观察细胞的存活和转归,从在体(in vivo)角度阐明MSCs在中枢神经系统疾病细胞治疗中的潜 在应用前景。首先用DiI在体外标记MSCs。将标记后的MSCs分别移植到大鼠纹状体和侧脑室, 在移植后2w和4w灌杀动物,进行脑组织及脊髓的冰冻切片,在荧光显微镜下观察细胞的存活与 转归。结果:移植到纹状体的MSCs可沿针道向周围实质迁移,迁移的最远距离可达0.2mm。并 且,在大脑皮层及其他脑实质的血管壁、血管中以及血管周围还可见到标记细胞;而移植到侧脑 室的MSCs则主要沿脑室系统迁移,细胞主要分布在移植侧侧脑室,对侧脑室与第四脑室也有分 布,也有少量细胞沿侧脑室向周围实质迁移,迁移的最远距离为0.23mm。还可见到沿胼胝体向 对侧脑室迁移的细胞流,甚至有个别细胞迁移至脊髓腰段。所有动物在细胞移植后4周均未发 现肿瘤形成。结论:MSCs脑内移植后可以在中枢神经系统内存活并迁移,无致瘤性。结果提示 骨髓间充质细胞是很多疾病细胞与基因治疗的有力工具。Objective: To demonstrate the potential application of mesenchymal stem cells (MSCs) in cell therapy for central nervous system disease. Methods: MSCs were labeled with DiI in vitro and transplanted into striatum and lateral ventricular of rats. Animals were sacrificed on day 14 and day 28 after implantation. Brains were sectioned and observed under the fluorescence microscope. Results: When MSCs were implanted in the striatum, they could diffuse around the transplanted points and migrate to the vascular of cortex; when MSCs were grafted in the lateral ventricular, they can migrate to the other lateral ventricular, the fourth ventricular and even spinal cord through the cerebral spinal fluid. There was no sarcoma formed in any experimental animal after 4 weeks. Conclusions: MSCs infused into rats brain can engraft, migrate, and survive. The results here supported that MSCs may be useful vehicles for both cell and gene therapy for a variety of diseases including Parkinson' s disease.

关 键 词：骨髓间充质干细胞 中枢神经系统疾病 MSCs 体内 侧脑室 stem 细胞治疗 冰冻切片 镜下观察 荧光显微 大脑皮层 标记细胞 系统迁移 细胞迁移 肿瘤形成 细胞移植 基因治疗 纹状体 存活 大鼠脑 DII 脑组织 血管壁 胼胝体 致瘤性 

分 类 号：Q813.11[生物学—生物工程] S858.23[农业科学—临床兽医学]