微泡
间充质干细胞
再生(生物学)
富血小板血浆
神经营养因子
细胞生物学
癌症研究
PI3K/AKT/mTOR通路
外体
化学
血小板
医学
免疫学
生物
信号转导
内科学
小RNA
生物化学
受体
基因
作者
Yongyi Zhang,Dan Yi,Quan Hong,Cao Jiang-bei,Geng Xu,Jinwei Liu,Chuang Xu,Cao Mengyu,Chao Chen,Xu Shuaixuan,Zhen Zhang,Molin Li,Yaqiong Zhu,Nan Peng
标识
DOI:10.1016/j.jconrel.2024.01.043
摘要
Peripheral nerve injury (PNI) remains a severe clinical problem with debilitating consequences. Mesenchymal stem cell (MSC)-based therapy is promising, but the problems of poor engraftment and insufficient neurotrophic effects need to be overcome. Herein, we isolated platelet-rich plasma-derived exosomes (PRP-Exos), which contain abundant bioactive molecules, and investigated their potential to increase the regenerative capacity of MSCs. We observed that PRP-Exos significantly increased MSC proliferation, viability, and mobility, decreased MSC apoptosis under stress, maintained MSC stemness, and attenuated MSC senescence. In vivo, PRP-Exo-treated MSCs (pExo-MSCs) exhibited an increased retention rate and heightened therapeutic efficacy, as indicated by increased axonal regeneration, remyelination, and recovery of neurological function in a PNI model. In vitro, pExo-MSCs coculture promoted Schwann cell proliferation and dorsal root ganglion axon growth. Moreover, the increased neurotrophic behaviour of pExo-MSCs was mediated by trophic factors, particularly glia-derived neurotrophic factor (GDNF), and PRP-Exos activated the PI3K/Akt signalling pathway in MSCs, leading to the observed phenotypes. These findings demonstrate that PRP-Exos may be novel agents for increasing the ability of MSCs to promote neural repair and regeneration in patients with PNI.
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