Mesenchymal stem cell-derived exosomes attenuate phosgene-induced acute lung injury in rats

Objective: We have previously found that mesenchymal stem cell (MSC) therapy can ameliorate phosgene-induced acute lung injury (ALI). Moreover, exosomes can be used as a cell-free alternative therapy. In the present study, we aimed to assess the effect of MSC-derived exosomes on phosgene-induced ALI.Methods: MSC-derived exosomes were isolated from MSCs through ultracentrifugation. Sprague-Dawley (SD) rats were exposed to phosgene at 8.33g/m(3) for 5min. MSC-derived exosomes were intratracheally administered and rats were sacrificed at the time points of 6, 24 and 48h.Results: Compared with the phosgene group, MSC-derived exosomes reversed respiratory function alterations, showing increased levels of TV, PIF, PEF and EF50 as well as decreased levels of RI and EEP. Furthermore, MSC-derived exosomes improved pathological alterations and reduced wet-to-dry ratio and total protein content in BALF. MSC-derived exosomes reduced the levels of TNF-alpha, IL-1 beta and IL-6 and increased the IL-10 level in BALF and plasma. MSC-derived exosomes suppressed the MMP-9 level and increased the SP-C level.Conclusions: MSC-derived exosomes exerted beneficial effects on phosgene-induced ALI via modulating inflammation, inhibiting MMP-9 synthesis and elevating SP-C level.