オオヤマ　ゲンコウ   OYAMA Genko   大山　彦光    所属   埼玉医科大学  医学部 脳神経内科    職種   教授
論文種別	学術雑誌(原著)
言語種別	英語
査読の有無	査読なし
表題	A defined method for differentiating human iPSCs into midbrain dopaminergic progenitors that safely restore motor deficits in Parkinson's disease.
掲載誌名	正式名：Frontiers in neuroscience
掲載区分	国外
巻・号・頁	17,1202027-1202027頁
著者・共著者	Ryota Nakamura,Risa Nonaka,Genko Oyama,Takayuki Jo,Hikaru Kamo,Maierdanjiang Nuermaimaiti,Wado Akamatsu,Kei-Ichi Ishikawa,Nobutaka Hattori
発行年月	2023
概要	BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative condition that primarily affects motor functions; it is caused by the loss of midbrain dopaminergic (mDA) neurons. The therapeutic effects of transplanting human-induced pluripotent stem cell (iPSC)-derived mDA neural progenitor cells in animal PD models are known and are being evaluated in an ongoing clinical trial. However, However, improvements in the safety and efficiency of differentiation-inducing methods are crucial for providing a larger scale of cell therapy studies. This study aimed to investigate the usefulness of dopaminergic progenitor cells derived from human iPSCs by our previously reported method, which promotes differentiation and neuronal maturation by treating iPSCs with three inhibitors at the start of induction. METHODS: Healthy subject-derived iPS cells were induced into mDA progenitor cells by the CTraS-mediated method we previously reported, and their proprieties and dopaminergic differentiation efficiency were examined in vitro. Then, the induced mDA progenitors were transplanted into 6-hydroxydopamine-lesioned PD model mice, and their efficacy in improving motor function, cell viability, and differentiation ability in vivo was evaluated for 16 weeks. RESULTS: Approximately ≥80% of cells induced by this method without sorting expressed mDA progenitor markers and differentiated primarily into A9 dopaminergic neurons in vitro. After transplantation in 6-hydroxydopamine-lesioned PD model mice, more than 90% of the engrafted cells differentiated into the lineage of mDA neurons, and approximately 15% developed into mature mDA neurons without tumour formation. The grafted PD model mice also demonstrated significantly improved motor functions. CONCLUSION: This study suggests that the differentiation protocol for the preparation of mDA progenitors is a promising option for cell therapy in patients with PD.
DOI	10.3389/fnins.2023.1202027
PMID	37502682