Role of miR‐466 in mesenchymal stromal cell derived extracellular vesicles treating inoculation pneumonia caused by multidrug‐resistant Pseudomonas aeruginosa

RATIONALE: The effects of mesenchymal stromal cells (MSCs) and MSC‐derived extracellular vesicles (MSC EVs) on multidrug‐resistant pseudomonas aeruginosa (MDR‐PA)‐induced pneumonia remain unclear. MATERIALS AND METHODS: MicroRNA array and RT‐PCR were used to select the major microRNA in MSC EVs. Human peripheral blood monocytes were obtained and isolated from qualified patients. The crosstalk between MSCs/MSC EVs and macrophages in vitro was studied. MDR‐PA pneumonia models were further established in C57BL/6 mice and MSC EVs or miR‐466 overexpressing MSC EVs were intratracheally instilled. RESULTS: MiR‐466 was highly expressed in MSC EVs. MSCs and miR‐466 promoted macrophage polarization toward Type 2 phenotype through TIRAP‐MyD88‐NFκB axis. Moreover, cocultured macrophages with miR‐466 overexpressing MSCs significantly increased the phagocytosis of macrophages. MSC EVs significantly reduced mortality and decreased influx of BALF neutrophils, proinflammatory factor levels, protein, and bacterial load in murine MDR‐PA pneumonia. Administration of miR‐466 overexpressing MSC EVs further alleviated the inflammatory severity. CONCLUSIONS: MSC‐derived EVs containing high levels of miR‐466 may partly participate in host immune responses to MDR‐PA. Both MSCs and MSC EVs have therapeutic effects in treating MDR‐PA‐induced pneumonia.