ESC-sEVs改善NSCs衰老促进老年脑卒中后神经再生的机制研究

缺血性脑卒中是严重威胁老年人群健康的脑血管疾病，切实改善老年脑卒中患者的预后是临床亟待解决的难题。我们的前期研究提示神经干细胞（NSCs）的衰老状态是影响老年脑卒中患者预后的关键因素。我们前期实验发现，胚胎干细胞来源的小细胞外囊泡（ESC-sEVs）可显著促进老年脑卒中后神经功能的恢复，其机制可能与其改善NSCs衰老状态有关，MYT1可能是调控NSCs衰老的关键分子；结合ESC-sEVs质谱分析及MYT1转录因子结合位点预测结果，我们推测ESCs-sEVs极有可能是通过转运OCT4等关键因子调控MYT1改善NSCs衰老状态，进而促进老年脑卒中后神经再生功能。据此，我们拟在前期研究基础上，通过系列实验阐明ESC-sEVs改善NSCs衰老、促进老年脑卒中神经功能修复的具体分子机制，为老年脑卒中的治疗研究提供新的理论依据和技术策略。

Ischemic stroke is a common cerebral vascular disease which severely threatens public health, mostly among aged population. However, how to improve the prognosis of the elderly patients is a critical problem and urgent question to be solved. Our previous study indicated that neural stem cells (NSCs) senescence played a key role in the neurological recovery in old patients after stroke. Furthermore, we also found that treatment with embryonic stem cells derived small extracellular vesicles (ESC-sEVs) remarkably facilitated neurofunctional recovery likely by the modulation of NSCs senescence in which MYT1 may be the crucial factor. In addition, combining the data from transcriptome analysis of ESC-sEVs and transcription factor binding site (TFBS) of MYT1, we speculated ESC-sEVs improve the status of NSCs senescence, neurogenesis ability, and neurological functions after ischemic stroke in the elderly through modulation of MYT1 in NSCs via the transfer of OCT4 or other key factors. Accordingly, based on these results, we aim to conduct the following studies to thoroughly explore the molecular mechanisms of ESC-sEVs in modulating NSCs senescence and improving neurological recovery after stroke, which may provide new perspectives to the development of treatment scheme for stroke in the elderly.