骨髓基质细胞移植治疗帕金森病恒河猴的实验研究

Bone marrow stromal cell transplantation for treatment of Parkinson＇s disease in rhesus monkeys

目的探讨以骨髓基质细胞（BMSCs）为供体移植治疗帕金森病（PD）模型恒河猴的可行性。方法应用立体定向手术毁损单侧黑质建立恒河猴PD模型，采用加拿大评分和单光子发射计算机断层成像术（SPECT）分别观察恒河猴行为学和大脑黑质多巴胺转运蛋白（DAT）的变化，免疫荧光双标染色检测恒河猴黑质移植侧和正常侧BMSCs的分化状态。结果移植BMSCs后恒河猴的PD综合征症状逐渐加重；SPECT检测显示恒河猴移植BMSCs前后黑质双侧DAT无明显变化，但免疫荧光显示移植后BMSCs分化为多巴胺（DA）能神经元的比例高达25％。结论BMSCs无法作为有效的移植供体治疗PD，其可行性尚需进一步研究。

Objective To evaluate the therapeutic effect of bone marrow stromal cell transplantation on Parkinson＇s disease （PD） in rhesus monkeys. Methods Experimental PD was induced in rhesus monkeys by stereotatie surgery to destroy the unilateral substantia nigra. Human bone marrow stromal ceils were injected stereotaxically into the 9 target areas in the brain of the monkeys, after which behavioral test was performed and the alteration in the dopamine transporter （DAT） in the substantia nigra was examined using single-photon emission computerized tomography （SPECT）. Immunofluorescence assay was employed to examine the TH- and BrdU-positive cells in the injured and contralateral substantia nigra. Results All the monkeys showed progressive deterioration of the PD symptoms after the cell transplantation. SPECT revealed no significant changes in DAT in the bilateral substantia nigra, but immunoflurescence assay showed that a proportion as high as 25% of the transplanted BMSCs differentiated into dopaminergic neurons. Conclusion Human BMSCs can not serve as the donor cells for treatment of PD in rhesus monkeys.