Extracellular Vesicles Derived from Human Adipose-Derived Mesenchymal Stem Cells Alleviate Sepsis-Induced Acute Lung Injury through a MicroRNA-150–5p-Dependent Mechanism
Chengkuan Zhao, Qianhua Luo, Jianxiang Huang, Siman Su, Lijuan Zhang, Danling Zheng, Meini Chen, Xinyue Lin, Jialin Zhong, Li Li, Kai Ling, Shuyao Zhang
Abstract
Extracellular vesicles (EVs) derived from human adipose mesenchymal stem cells (hADSCs) may exert a therapeutic benefit in alleviating sepsis-induced organ dysfunction by delivering cargos that include RNAs and proteins to target cells. The current study aims to explore the protective effect of miR-150–5p delivered by hADSC-EVs on sepsis-induced acute lung injury (ALI). We noted low expression of miR-150–5p in plasma and bronchoalveolar lavage fluid samples from patients with sepsis-induced ALI. The hADSC-EVs were isolated and subsequently cocultured with macrophages. It was established that hADSC-EVs transferred miR-150–5p to macrophages, where miR-150–5p targeted HMGA2 to inhibit its expression and, consequently, inactivated the MAPK pathway. This effect contributed to the promotion of M2 polarization of macrophages and the inhibition of proinflammatory cytokines. Further, mice were made septic by cecal ligation and puncture in vivo and treated with hADSC-EVs to elucidate the effect of hADSC-EVs on sepsis-induced ALI. The in vivo experimental results confirmed a suppressive role of hADSC-EVs in sepsis-induced ALI. Our findings suggest that hADSC-EV-mediated transfer of miR-150–5p may be a novel mechanism underlying the paracrine effects of hADSC-EVs on the M2 polarization of macrophages in sepsis-induced ALI.