神经科学
星形胶质细胞
少突胶质细胞
祖细胞
诱导多能干细胞
生物
医学
再髓鞘化
白质
髓鞘
神经干细胞
细胞生物学
干细胞
中枢神经系统
胚胎干细胞
遗传学
磁共振成像
放射科
基因
作者
Irene L. Llorente,Yuan Xie,Jose A. Mazzitelli,Emily A. Hatanaka,Jessica Cinkornpumin,David R. Miller,Ying Lin,William E. Lowry,S. Thomas Carmichael
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2021-04-21
卷期号:13 (590)
被引量:32
标识
DOI:10.1126/scitranslmed.aaz6747
摘要
Subcortical white matter stroke (WMS) accounts for up to 30% of all stroke events. WMS damages primarily astrocytes, axons, oligodendrocytes, and myelin. We hypothesized that a therapeutic intervention targeting astrocytes would be ideally suited for brain repair after WMS. We characterize the cellular properties and in vivo tissue repair activity of glial enriched progenitor (GEP) cells differentiated from human-induced pluripotent stem cells, termed hiPSC-derived GEPs (hiPSC-GEPs). hiPSC-GEPs are derived from hiPSC-neural progenitor cells via an experimental manipulation of hypoxia inducible factor activity by brief treatment with a prolyl hydroxylase inhibitor, deferoxamine. This treatment permanently biases these cells to further differentiate toward an astrocyte fate. hiPSC-GEPs transplanted into the brain in the subacute period after WMS in mice migrated widely, matured into astrocytes with a prorepair phenotype, induced endogenous oligodendrocyte precursor proliferation and remyelination, and promoted axonal sprouting. hiPSC-GEPs enhanced motor and cognitive recovery compared to other hiPSC-differentiated cell types. This approach establishes an hiPSC-derived product with easy scale-up capabilities that might be effective for treating WMS.
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