Department of Sleep Medicine Center, The Shengjing Affiliated Hospital, China Medical University, Shenyang 110004, Liaoning, PR China.
Department of Neurology/Stroke Center, the First Affiliated Hospital of China Medical University, China Medical University, Shenyang 110001, Liaoning, PR China.
Cell Signal. 2024 Jul;119:111146. doi: 10.1016/j.cellsig.2024.111146. Epub 2024 Mar 16.
Intracerebral hemorrhage (ICH) is associated with secondary neuroinflammation, leading to severe central nervous system damage. Exosomes derived from human adipose-derived mesenchymal stem cells (hADSCs-Exo) have shown potential therapeutic effects in regulating inflammatory responses in ICH. This study aims to investigate the role of hADSCs-Exo in ICH and its underlying mechanism involving miRNA-mediated regulation of formyl peptide receptor 1 (FPR1). Flow cytometry was used to identify hADSCs and extract exosomes. Transmission electron microscopy and Western blot were performed to confirm the characteristics of the exosomes. In vitro experiments were conducted to explore the uptake of hADSCs-Exo by microglia cells and their impact on inflammatory responses. In vivo, an ICH mouse model was established, and the therapeutic effects of hADSCs-Exo were evaluated through neurological function scoring, histological staining, and immunofluorescence. Bioinformatics tools and experimental validation were employed to identify miRNAs targeting FPR1. hADSCs-Exo were efficiently taken up by microglia cells and exhibited anti-inflammatory effects by suppressing the release of inflammatory factors and promoting M1 to M2 transition. In the ICH mouse model, hADSCs-Exo significantly improved neurological function, reduced hemorrhage volume, decreased neuronal apoptosis, and regulated microglia polarization. miR-342-3p was identified as a potential regulator of FPR1 involved in the neuroprotective effects of hADSCs-Exo in ICH. hADSCs-Exo alleviate neuroinflammation in ICH through miR-342-3p-dependent targeting of FPR1, providing a new therapeutic strategy for ICH.
脑出血（ICH）与继发性神经炎症有关，导致严重的中枢神经系统损伤。源自人脂肪间充质干细胞（hADSCs-Exo）的外泌体在调节 ICH 中的炎症反应方面显示出潜在的治疗效果。本研究旨在探讨 hADSCs-Exo 在 ICH 中的作用及其潜在机制，涉及 miRNA 介导的对甲酰肽受体 1（FPR1）的调节。流式细胞术用于鉴定 hADSCs 并提取外泌体。透射电子显微镜和 Western blot 用于确认外泌体的特征。体外实验用于探索 hADSCs-Exo 被小胶质细胞摄取及其对炎症反应的影响。在体内，建立 ICH 小鼠模型，并通过神经功能评分、组织学染色和免疫荧光评估 hADSCs-Exo 的治疗效果。生物信息学工具和实验验证用于鉴定靶向 FPR1 的 miRNAs。hADSCs-Exo 被小胶质细胞有效摄取，并通过抑制炎症因子的释放和促进 M1 向 M2 转化发挥抗炎作用。在 ICH 小鼠模型中，hADSCs-Exo 显著改善神经功能，减少出血体积，减少神经元凋亡，并调节小胶质细胞极化。miR-342-3p 被鉴定为参与 hADSCs-Exo 在 ICH 中神经保护作用的 FPR1 的潜在调节剂。hADSCs-Exo 通过 miR-342-3p 依赖的 FPR1 靶向减轻 ICH 中的神经炎症，为 ICH 提供了一种新的治疗策略。
