骨髓间充质干细胞移植治疗Tourette综合征大鼠实验研究

Transplantation of bone marrow mesenchymal stem cells in rat model of Tourette syndrome

目的考察骨髓间充质干细胞（Mescenchymal Stem Cell，MSC）移植治疗Tourette综合征（Tourette syndrome，TS）大鼠的可行性及其作用机制。方法建立TS大鼠自身免疫动物模型，采用立体定向脑内注射法将用BrdU标记的MSC移植到TS大鼠纹状体内，观察大鼠刻板行为改善情况。通过免疫组化双染分析MSC在TS大鼠脑内存活、分化情况。结果流式细胞仪示MSC表面标记阳性率CD2995．2％，CD4496．3％，CD10597．2％，CD10694．1％。MSC移植组大鼠在细胞移植后10d和14d的刻板行为总分[分别为（95．5±6．6）分、（73．1±6．5）分]低于对照组[（114．1±6．0）分、（108．0±6．4）分]，差异具有显著性（P〈0．01）。MSC在TS大鼠脑内生长存活并分化为神经前体细胞、神经元或星形胶质细胞。结论纹状体内MSC移植可减少TS大鼠的刻板行为。MSC移植可能对TS具有一定的治疗作用。

Objective To investigate the effect of mescenchymal stem cell （MSC） transplantation on Tourette syndrome （TS） model rats. Methods Stereotypies can be successfully induced in rats by intrastriatal microinfusion of TS sera. MSC suspension was bilaterally injected into the striatum. Survival and differentiation of transplanted MSC were tested through immunohistochemical analyses. Results Flow cytometry results demonstrated that the ceils strongly expressed CD29（95.2% ） ,CD105（97.2% ） ,CIM4（96.3% ） and CD106 （94.1%）. TS rats with MSC grafts exhibited significantly decreased stereotypic behaviors at 10 and 14 days（95.5 ±6.6,73. 1 ±6.5 vs. 114.1 ± 6.0,108.0 ± 6.4 ）. Immunohistochemistry analyses revealed survival of transplanted MSC and differentiation into neurons and astrocytes in the rat brain. Conclusion Intrastriatal transplantation of human MSC can provide therapeutic potential for TS.