Departments of Neurology, Pathology and Cell Biology, and Neuroscience, Columbia University, New York, New York, USA.
Department of Clinical Neuroscience and WT-MRC Cambridge Stem Cell Institute, University of Cambridge and Addenbrooke's Hospital, Cambridge, United Kingdom.
Mov Disord. 2021 Aug;36(8):1772-1780. doi: 10.1002/mds.28628. Epub 2021 May 8.
The last decade has seen exciting advances in the development of potential stem cell-based therapies for Parkinson's disease (PD), which have used different types of stem cells as starting material. These cells have been developed primarily to replace dopamine-producing neurons in the substantia nigra that are progressively lost in the disease process. The aim is to largely restore lost motor functions, whilst not ever being curative. We discuss cell-based strategies that will have to fulfill important criteria to become effective and competitive therapies for PD. These criteria include reproducibly producing sufficient numbers of cells with an authentic substantia nigra dopamine neuron A9 phenotype, which can integrate into the host brain after transplantation and form synapses (considered crucial for long-term functional benefits). Furthermore, it is essential that transplanted cells exhibit no, or only very low levels of, proliferation without tumor formation at the site of grafting. Cumulative research has shown that stem cell-based approaches continue to have great potential in PD, but key questions remain to be answered. Here, we review the most recent progress in research on stem cell-based dopamine neuron replacement therapy for PD and briefly discuss what the immediate future might hold. © 2021 International Parkinson and Movement Disorder Society.
在过去的十年中，基于干细胞的潜在帕金森病（PD）治疗方法取得了令人兴奋的进展，这些方法使用了不同类型的干细胞作为起始材料。这些细胞主要是为了替代在疾病过程中逐渐丧失的黑质中产生多巴胺的神经元而开发的。其目的是在很大程度上恢复丧失的运动功能，而不是根治疾病。我们讨论了细胞为基础的策略，这些策略将必须满足重要的标准，才能成为有效的、有竞争力的 PD 治疗方法。这些标准包括可重复性地产生具有真正的黑质多巴胺神经元 A9 表型的足够数量的细胞，这些细胞在移植后可以整合到宿主大脑中并形成突触（被认为对长期功能益处至关重要）。此外，至关重要的是，移植细胞不应增殖或只有非常低水平的增殖，而不会在移植物部位形成肿瘤。累积的研究表明，基于干细胞的方法在 PD 中仍然具有很大的潜力，但仍有一些关键问题需要解答。在这里，我们回顾了基于干细胞的多巴胺神经元替代疗法治疗 PD 的最新研究进展，并简要讨论了近期的前景。© 2021 国际帕金森病和运动障碍学会。
