Open AccessRole of miR‐466 in mesenchymal stromal cell derived extracellular vesicles treating inoculation pneumonia caused by multidrug‐resistant Pseudomonas aeruginosa
Author(s) -
Shi Mengmeng,
Zhu Yinggang,
Yan Jiayang,
Rouby JeanJacques,
Summah Hanssa,
Monsel Antoine,
Qu Jieming
Publication year - 2021
Publication title -
clinical and translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
H-Index - 1
ISSN - 2001-1326
DOI - 10.1002/ctm2.287
Subject(s) - mesenchymal stem cell , proinflammatory cytokine , immune system , pseudomonas aeruginosa , microvesicles , exosome , multiple drug resistance , pneumonia , medicine , stromal cell , extracellular vesicle , microbiology and biotechnology , immunology , microrna , cancer research , biology , inflammation , drug resistance , pathology , biochemistry , bacteria , gene , genetics
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.