Healthy young human plasma-derived exosomes enhance neural stem cell therapy by suppressing pyroptosis via TXNIP/NLRP3 after intracerebral hemorrhage

作者：Jiao Chen, Ziqiang Chen, Fuan Zhang, Pangbo Wang, Q. Zhang, Haomiao Wang, Fengchun Zhao, Huanhuan Li, Ran Luo, Ning Ding, Shengtao Yao, Rong Hu · 发表于：Journal of Nanobiotechnology · 年份：2026 · DOI：10.1186/s12951-026-04099-6 · 被引用次数：1 · 研究领域：Inflammasome and immune disorders、Intracerebral and Subarachnoid Hemorrhage Research、Extracellular vesicles in disease

BACKGROUND: Neural stem cells (NSCs) transplantation holds promise for intracerebral hemorrhage (ICH) treatment, but its efficacy is limited by poor survival and aberrant differentiation of grafted cells. Here, we demonstrate that exosomes derived from healthy young donor plasma, a natural nanomaterial protect NSCs against pyroptosis, a gasdermin-dependent inflammatory cell death process triggered by ICH. METHODS: Plasma exosomes were extracted from young (Y-exo) and old (O-exo) healthy individuals and characterized. An in vitro model of ICH was established by hemin treatment. For the in vivo study, the mouse ICH model was induced by autologous blood, a combined transplantation of Y-exo and NSCs was then performed as the therapeutic intervention. The protective effects of exosomes on NSCs were assessed via western blotting, immunofluorescence, ELISA, qPCR, and Calcein/PI detection. The therapeutic effects of combined transplantation of Y-exo and NSCs on ICH mice were evaluated through in vivo imaging systems and a series of behavioral tests. RESULTS: Exosomes derived from young plasma exert protective effects by supporting NSC survival, boosting their proliferative and differentiation capacity in vitro, and ameliorating the peri-hematoma microenvironment in vivo. Strikingly, the efficacy of Y-exo is superior to that of O-exo. Subsequent studies will use Y-exo, in vitro, the Y-exo exerted their protective effects by inhibiting the NLRP3/Caspase-1/GSDMD-mediated pyroptotic path...