诱导多能干细胞衍生的多巴胺能祖细胞治疗帕金森病的临床前研究。
Pre-clinical study of induced pluripotent stem cell-derived dopaminergic progenitor cells for Parkinson's disease.
机构信息
Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
Drug Safety Research Laboratories, Shin Nippon Biomedical Laboratories, Ltd, Kagoshima, Japan.
出版信息
Nat Commun. 2020 Jul 6;11(1):3369. doi: 10.1038/s41467-020-17165-w.
Induced pluripotent stem cell (iPSC)-derived dopaminergic (DA) neurons are an expected source for cell-based therapies for Parkinson's disease (PD). The regulatory criteria for the clinical application of these therapies, however, have not been established. Here we show the results of our pre-clinical study, in which we evaluate the safety and efficacy of dopaminergic progenitors (DAPs) derived from a clinical-grade human iPSC line. We confirm the characteristics of DAPs by in vitro analyses. We also verify that the DAP population include no residual undifferentiated iPSCs or early neural stem cells and have no genetic aberration in cancer-related genes. Furthermore, in vivo studies using immunodeficient mice reveal no tumorigenicity or toxicity of the cells. When the DAPs are transplanted into the striatum of 6-OHDA-lesioned rats, the animals show behavioral improvement. Based on these results, we started a clinical trial to treat PD patients in 2018.
诱导多能干细胞（iPSC）衍生的多巴胺能（DA）神经元有望成为帕金森病（PD）细胞治疗的来源。然而，这些治疗方法的临床应用的监管标准尚未建立。在这里，我们展示了我们的临床前研究结果，其中我们评估了源自临床级人 iPSC 系的多巴胺能祖细胞（DAP）的安全性和有效性。我们通过体外分析确认了 DAP 的特征。我们还验证了 DAP 群体中没有残留的未分化 iPSC 或早期神经干细胞，并且在与癌症相关的基因中没有遗传异常。此外，使用免疫缺陷小鼠的体内研究表明细胞没有致瘤性或毒性。当将 DAP 移植到 6-OHDA 损伤的大鼠纹状体中时，动物表现出行为改善。基于这些结果，我们于 2018 年开始了一项治疗 PD 患者的临床试验。
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