There is escalating interest in cell-based therapies to restore lost dopamine inputs in Parkinson’s disease. This is based upon the rationale that implanting dopamine progenitors into the striatum can potentially improve dopamine-responsive motor symptoms. A rich body of data describing clinical trials of previous cell transplantation exists. These have included multiple cell sources for transplantation including allogeneic (human embryonic mesencephalic tissue, retinal pigment epithelial cells) and autologous (carotid body, adrenal medullary tissue) cells, as well as xenotransplantation. However, there are multiple limitations related to these cell sources, including availability of adequate numbers of cells for transplant, heterogeneity within cells transplanted, imprecisely defined mechanisms of action, and poor cell survival after transplantation in some cases. Nonetheless, evidence has accrued from a subset of trials to support the rationale for such a regenerative approach. Recent rapid advances in stem cell technology may now overcome these prior limitations. For example, dopamine neuron precursor cells for transplant can be generated from induced pluripotent cells and human embryonic stem cells. The benefits of these innovative approaches include: the possibility of scalability; a high degree of quality control; and improved understanding of mechanisms of action with rigorous preclinical testing. In this review, we focus on the potential for cell-based therapies in Parkinson’s disease to restore the function of dopaminergic neurons, we critically review previous attempts to harness such strategies, we discuss potential benefits and predicted limitations, and we address how previous roadblocks may be overcome to bring a cell-based approach to the clinic.

人们对基于细胞的疗法越来越感兴趣，以恢复帕金森病中丢失的多巴胺输入。这是基于将多巴胺祖细胞植入纹状体可以潜在地改善多巴胺反应性运动症状的基本原理。存在大量描述先前细胞移植临床试验的数据。这些包括用于移植的多种细胞来源，包括同种异体（人胚胎中脑组织、视网膜色素上皮细胞）和自体（颈动脉体、肾上腺髓质组织）细胞，以及异种移植。然而，这些细胞来源存在多种限制，包括可用于移植的足够数量的细胞、移植细胞内的异质性、不精确定义的作用机制、在某些情况下，移植后细胞存活率低。尽管如此，从一部分试验中获得的证据支持这种再生方法的基本原理。最近干细胞技术的快速进步现在可能会克服这些先前的限制。例如，用于移植的多巴胺神经元前体细胞可以从诱导多能细胞和人类胚胎干细胞中产生。这些创新方法的好处包括： 可扩展性的可能性；高度的质量控制；并通过严格的临床前测试提高对作用机制的理解。在这篇综述中，我们重点关注基于细胞的疗法在帕金森病中恢复多巴胺能神经元功能的潜力，我们批判性地回顾了以前利用这些策略的尝试，