多巴胺神经元联合中脑神经干细胞移植治疗帕金森病

Transplantation of Dopaminergic Neurons in Combination with Mesencephalic Neural Stem Cells for Parkinson's Disease

目的探讨多巴胺神经元联合中脑神经干细胞移植治疗帕金森病大鼠的作用效果。方法体外分离大鼠胚胎腹侧中脑神经干细胞并行增强型绿色荧光蛋白(EGFP)修饰。分离大鼠胚胎多巴胺神经元,并用CM-Di I染料标记。构建经典的6-羟多巴胺毁损帕金森病大鼠模型。采用立体定向注射技术,将细胞移植到帕金森病大鼠纹状体区,阿朴吗啡(APO)腹腔注射诱导其偏侧旋转,评估细胞移植后运动障碍改善情况。采用免疫荧光组织化学鉴定移植细胞的定植存活、迁移及分化。结果细胞移植能显著改善帕金森病大鼠的运动障碍,以多巴胺神经元联合中脑神经干细胞移植(联合移植组)治疗最为显著,有更多的神经干细胞分化为多巴胺神经元。绝大多数移植细胞停留在移植部位,仅极少数向周围脑区迁移。结论多巴胺神经元联合神经干细胞移植治疗帕金森病大鼠可显著改善其运动障碍,其具体相关分子机制还有待进一步研究。

Objective To explore the therapeutic effect of intracerebral transplantation of dopaminergic（DA） neurons in combination with ventral mesencephalic neural stem cells（m NSC） for Parkinson＇s disease（PD）. Methods The rat embryonic m NSCs were isolated in vitro, and modified with enhanced green fluorescent protein（EGFP）. The rat embryonic DA neurons were isolated, and labeled with CM-Di I. The classical 6-hydrodopamine damage models of PD rats were established. Then the cells were transplanted into the striatum of PD rats by stereotactic injection. The lateral rotations were induced by intraperitoneal injection of apomorphine（APO）, and the improvements of movement disorders were evaluated. The survival, migration and differentiation of transplanted cells were identified by immunofluorescence histochemistry. Results The movement disorders were obviously improved by cell transplantation in PD rats, and the therapeutic efficacy of cotransplantation of DA neurons and m NSCs（cotransplantation group） was the most striking. With cotransplantation, more m NSCs were differentiated into DA neurons. Most transplanted cells stayed in the transplant areas, while a very few cells migrated to the surrounding areas. Conclusions The intracerebral transplantation of DA neurons in combination with m NSCs can considerably improve the movement disorders of PD rats. However, the molecular mechanism remains to be further studied.