Data_Sheet_3_Postmortem Studies of Fetal Grafts in Parkinson’s Disease: What Lessons Have We Learned?.PDF

Neural transplantation is a potential therapeutic method for Parkinson’s disease (PD). Fetal dopaminergic (DA) neurons have been important transplantation cell sources in the history of replacement therapy for PD. Several decades of preclinical animal experiments and clinical trials using fetal DA neuron transplantation in PD therapy have shown not only promising results but also problems. In order to reveal possible factors influencing the clinical outcomes, we reviewed fetal DA neuron transplantation therapies from 1970s to present, with a special focus on postmortem studies. Firstly, we gave a general description of the clinical outcomes and neuroanatomy of grafted cases; secondly, we summarized the main available postmortem studies, including the cell survival, reinnervation, and pathology development. In the end, we further discussed the link between function and structure of the grafts, seeking for the possible factors contributing to a functional graft. With our review, we hope to provide references for future transplantation trials from a histological point of view.

神经移植是治疗帕金森病（Parkinson’s Disease，PD）的潜在疗法。胎儿多巴胺能（dopaminergic，DA）神经元一直是PD替代治疗历史中重要的移植细胞来源。数十年来，在PD治疗中采用胎儿DA神经元移植的临床前动物实验与临床试验，不仅展现出颇具前景的治疗效果，同时也暴露出诸多亟待解决的问题。为揭示影响临床结局的潜在因素，本研究回顾了1970年代至今的胎儿DA神经元移植疗法，尤其聚焦于尸检研究（postmortem studies）。首先，本研究对移植病例的临床结局与神经解剖学特征进行了系统性概述；其次，梳理了现有主要的尸检研究成果，涵盖细胞存活、神经再支配以及病理进展三个维度。最后，本研究进一步探讨了移植物的功能与结构之间的关联，以期探寻可促成功能性移植物的潜在影响因素。本综述旨在从组织学视角为未来的移植临床试验提供参考依据。