Isacson Ole, Bjorklund Lars M, Schumacher James M
Udall Parkinson's Disease Research Center of Excellence, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA.
Ann Neurol. 2003;53 Suppl 3:S135-46; discussion S146-8. doi: 10.1002/ana.10482.
New therapeutic nonpharmacological methodology in Parkinson's disease (PD) involves cell and synaptic renewal or replacement to restore function of neuronal systems, including the dopaminergic (DA) system. Using fetal DA cell therapy in PD patients and laboratory models, it has been demonstrated that functional motor deficits associated with parkinsonism can be reduced. Similar results have been observed in animal models with stem cell-derived DA neurons. Evidence obtained from transplanted PD patients further shows that the underlying disease process does not destroy transplanted fetal DA cells, although degeneration of the host nigrostriatal system continues. The optimal DA cell regeneration system would reconstitute a normal neuronal network capable of restoring feedback-controlled release of DA in the nigrostriatal system. The success of cell therapy for PD is limited by access to preparation and development of highly specialized dopaminergic neurons found in the A9 and A10 region of the substantia nigra pars compacta as well as the technical and surgical steps associated with the transplantation procedure. Recent laboratory work has focused on using stem cells as a starting point for deriving the optimal DA cells to restore the nigrostriatal system. Ultimately, understanding the cell biological principles necessary for generating functional DA neurons can provide many new avenues for better treatment of patients with PD.
帕金森病（PD）新的治疗性非药物方法涉及细胞和突触的更新或替代，以恢复包括多巴胺能（DA）系统在内的神经元系统的功能。通过在帕金森病患者和实验室模型中使用胎儿多巴胺能细胞疗法，已证明与帕金森症相关的功能性运动缺陷可以减少。在具有干细胞衍生的多巴胺能神经元的动物模型中也观察到了类似的结果。从接受移植的帕金森病患者获得的证据进一步表明，尽管宿主黑质纹状体系统持续退化，但潜在的疾病过程并不会破坏移植的胎儿多巴胺能细胞。最佳的多巴胺能细胞再生系统将重建一个能够恢复黑质纹状体系统中多巴胺反馈控制释放的正常神经网络。帕金森病细胞治疗的成功受到获取制备和培养黑质致密部A9和A10区域中高度专业化的多巴胺能神经元的限制，以及与移植程序相关的技术和手术步骤的限制。最近的实验室工作集中在使用干细胞作为起点来衍生最佳的多巴胺能细胞，以恢复黑质纹状体系统。最终，了解生成功能性多巴胺能神经元所需的细胞生物学原理可以为更好地治疗帕金森病患者提供许多新途径。
