期刊
STEM CELLS TRANSLATIONAL MEDICINE
卷 10, 期 2, 页码 278-290出版社
OXFORD UNIV PRESS
DOI: 10.1002/sctm.20-0014
关键词
cell transplantation; immune-deficient models; iPSCs; Parkinson's disease
资金
- Fujifilm Cellular Dynamics, Inc
This study presents effective non-genetic methods to restrain cell proliferation when generating dopamine neurons for Parkinson's disease transplantation, suggesting that the use of MMC can successfully reduce proliferation without compromising long-term survival and function of the grafts.
Nongenetic methodologies to reduce undesirable proliferation would be valuable when generating dopamine neurons from stem cells for transplantation in Parkinson's disease (PD). To this end, we modified an established method for controlled differentiation of human induced pluripotent stem cells (iPSCs) into midbrain dopamine neurons using two distinct methods: omission of FGF8 or the in-process use of the DNA cross-linker mitomycin-C (MMC). We transplanted the cells to athymic rats with unilateral 6-hydroxydopamine lesions and monitored long-term survival and function of the grafts. Transplants of cells manufactured using MMC had low proliferation while still permitting robust survival and function comparable to that seen with transplanted dopamine neurons derived using genetic drug selection. Conversely, cells manufactured without FGF8 survived transplantation but exhibited poor in vivo function. Our results suggest that MMC can be used to reduce the number of proliferative cells in stem cell-derived postmitotic neuron preparations for use in PD cell therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据