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
| Autor: | Jianbang Han, Xiao-dan Jiang, Zhongfei Zhang, Qian Ouyang, Zhiming Feng, Zhizheng Liu, Haitao Sun, Tian Hua, Yan-ping Tang, Feng Li, Yu Xie, Bingke Lv, Xiaoxiong Zou, Ying-qian Cai, Shiting Hua, Run Zhang, Yu-xi Zou |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
mesenchymal stem/stromal cell
Aging Inflammation exosomes Exosome Neuroprotection neuroinflammation Umbilical Cord Brain ischemia Mice medicine ischemic stroke Animals Humans Neuroinflammation Microglia microRNA business.industry Mesenchymal stem cell fungi Intracellular Signaling Peptides and Proteins Mesenchymal Stem Cells Cell Biology medicine.disease carbohydrates (lipids) Disease Models Animal MicroRNAs medicine.anatomical_structure Interleukin-1 Receptor-Associated Kinases Cancer research medicine.symptom Stem cell business Research Paper Signal Transduction |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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