Stoker Thomas B, Blair Nicholas F, Barker Roger A
John van Geest Center for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK.
Neural Regen Res. 2017 Mar;12(3):389-392. doi: 10.4103/1673-5374.202935.
Parkinson's disease (PD) is a neurodegenerative condition which causes a characteristic movement disorder secondary to loss of dopaminergic neurons in the substanitia nigra. The motor disorder responds well to dopamine-replacement therapies, though these result in significant adverse effects due to non-physiological release of dopamine in the striatum, and off-target effects. Cell-based regenerative treatments offer a potential means for targeted replacement of dopamine, in a physiological manner. Dopaminergic neurons for cell-based therapies can be obtained from several sources. Fetal ventral mesencephalon tissue contains dopaminergic neuron progenitors, and has been transplanted into the striatum of PD patients with good results in a number of cases. However, the ethical implications and logistical challenges of using fetal tissue mean that fetal ventral mesencephalon is unlikely to be used in a widespread clinical setting. Induced pluripotent stem cells can be used to generate dopaminergic neurons for transplantation, providing a source of autologous tissue for grafting. This approach means that challenges associated with allografts, such as the potential for immune rejection, can be circumvented. However, the associated cost and difficulty in producing a standardized product from different cell lines means that, at present, this approach is not commercially viable as a cell-based therapy. Dopaminergic neurons derived from embryonic stem cells offer the most promising basis for a cell-based therapy for Parkinson's disease, with trials due to commence in the next few years. Though there are ethical considerations to take into account when using embryonic tissue, the possibility of producing a standardized, optimized cell product means that this approach can be both effective, and commercially viable.
帕金森病（PD）是一种神经退行性疾病，由于黑质中多巴胺能神经元的丧失，导致特征性的运动障碍。运动障碍对多巴胺替代疗法反应良好，尽管这些疗法由于纹状体中多巴胺的非生理性释放和脱靶效应而导致显著的不良反应。基于细胞的再生治疗提供了一种以生理方式靶向替代多巴胺的潜在方法。用于细胞治疗的多巴胺能神经元可以从多种来源获得。胎儿腹侧中脑组织含有多巴胺能神经元祖细胞，已被移植到帕金森病患者的纹状体中，在许多病例中取得了良好的效果。然而，使用胎儿组织的伦理问题和后勤挑战意味着胎儿腹侧中脑不太可能在广泛的临床环境中使用。诱导多能干细胞可用于生成用于移植的多巴胺能神经元，为移植提供自体组织来源。这种方法意味着可以规避与同种异体移植相关的挑战，例如免疫排斥的可能性。然而，从不同细胞系生产标准化产品的相关成本和难度意味着，目前这种方法作为基于细胞的治疗在商业上不可行。源自胚胎干细胞的多巴胺能神经元为帕金森病的基于细胞的治疗提供了最有前景的基础，试验将于未来几年开始。尽管在使用胚胎组织时需要考虑伦理问题，但生产标准化、优化的细胞产品的可能性意味着这种方法既有效又具有商业可行性。
