Neural stem cell-derived extracellular vesicles mitigate Alzheimer’s disease-like phenotypes in a preclinical mouse model
Ge Gao, Congcong Li, Yizhao Ma, Zhanping Liang, Yun Li, Xiangyu Li, Shengyang Fu, Yi Wang, Xiaohuan Xia, Jialin Zheng
Abstract
Alzheimer’s disease (AD) is the most common neurodegenerative disorder and the No.1 cause of dementia in elderly with no effective treatments. 1 The application of stem cell-derived extracellular vesicles (EVs) has emerged as a promising therapeutic strategy for AD. 2 EVs are small bilipid layer-enclosed vesicles that display blood-brain barrier (BBB) penetrating ability and similar potency to their parental cells. 2 The administration of EVs derived from neural stem cells (NSCs) and mesenchymal stem cell (MSCs) improved learning and memory functions of AD mice after EVs injection. 2 NSC-derived EVs (NSC-EVs) have been reported to show better effects on improving neural recovery than MSC-derived EVs. 3 However, due to ethical/religious concerns, supply constraints, limited expandability in culture, genetic/phenotypic instability issues, and potential immune responses of allogenic cell secretomes, NSCs may not be an excellent cell source for the production of clinical-grade EVs. Our previous studies obtained mouse fibroblast-derived induced NSCs (iNSCs) through somatic cell reprogramming, opening a new window for obtaining EVs derived from NSC-like cells. 4 , 5 However, whether iNSC-derived (iNSC-EVs) can serve as promising substitutes of NSC-EVs in AD treatment remains unclear.