Human umbilical cord mesenchymal stem cell-derived exosomal miR-146a-5p reduces microglial-mediated neuroinflammation via suppression of the IRAK1/TRAF6 signaling pathway after ischemic stroke.
Human umbilical cord mesenchymal stem cell-derived exosomal miR-146a-5p reduces microglial-mediated neuroinflammation via suppression of the IRAK1/TRAF6 signaling pathway after ischemic stroke.
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人脐带间充质干细胞来源的外泌体 miR-146a-5p 通过抑制缺血性中风后的 IRAK1/TRAF6 信号通路来减少小胶质细胞介导的神经炎症。
DOI：
10.18632/aging.202466
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发表时间：
2021-01-21
期刊：
影响因子：
--
通讯作者：
Jiang X
中科院分区：
文献类型：
--
作者：
Zhang Z;Zou X;Zhang R;Xie Y;Feng Z;Li F;Han J;Sun H;Ouyang Q;Hua S;Lv B;Hua T;Liu Z;Cai Y;Zou Y;Tang Y;Jiang X
为了研究移植干细胞的治疗机制并开发基于外泌体的纳米疗法治疗缺血性中风，我们评估了人脐带间充质干细胞（hUMC）产生的外泌体（Exos）对缺血性中风后小胶质细胞介导的神经炎症的作用。我们的结果发现，注射的 hUMSC-Exos 能够到达缺血损伤部位，并且可以在体内和体外被细胞内化。在体外，hUMSC-Exos 治疗可减轻氧糖剥夺 (OGD) 后小胶质细胞介导的炎症。体内结果表明，根据短暂性脑缺血三天后的测量结果，hUMSC-Exos 治疗可显着减少梗塞体积、减轻行为缺陷并改善小胶质细胞活化。此外，miR-146a-5p 敲低（miR-146a-5p k/d Exos）部分逆转了 hUMSC-Exos 的神经保护作用。我们的机制研究表明，hUMSC-Exos 中的 miR-146a-5p 通过 IRAK1/TRAF6 途径减少小胶质细胞介导的神经炎症反应。我们得出的结论是，源自 hUMSC-Exos 的 miR-146a-5p 可以减轻小胶质细胞介导的神经炎症和缺血性中风后随之而来的神经缺陷。这些结果阐明了间充质干细胞的潜在治疗机制，并提供了 hUMSC-Exos 代表缺血性中风的潜在无细胞治疗选择的证据。
To investigate the therapeutic mechanism of action of transplanted stem cells and develop exosome-based nanotherapeutics for ischemic stroke, we assessed the effect of exosomes (Exos) produced by human umbilical cord mesenchymal stem cells (hUMSCs) on microglia-mediated neuroinflammation after ischemic stroke. Our results found that injected hUMSC-Exos were able to access the site of ischemic damage and could be internalized by cells both in vivo and in vitro. In vitro, treatment with hUMSC-Exos attenuated microglia-mediated inflammation after oxygen-glucose deprivation (OGD). In vivo results demonstrated that treatment with hUMSC-Exos significantly reduced infarct volume, attenuated behavioral deficits, and ameliorated microglia activation, as measured three days post-transient brain ischemia. Furthermore, miR-146a-5p knockdown (miR-146a-5p k/d Exos) partially reversed the neuroprotective effect of hUMSC-Exos. Our mechanistic study demonstrated that miR-146a-5p in hUMSC-Exos reduces microglial-mediated neuroinflammatory response through IRAK1/TRAF6 pathway. We conclude that miR-146a-5p derived from hUMSC-Exos can attenuate microglia-mediated neuroinflammation and consequent neural deficits following ischemic stroke. These results elucidate a potential therapeutic mechanism of action of mesenchymal stem cells and provide evidence that hUMSC-Exos represent a potential cell-free therapeutic option for ischemic stroke.
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