Mesenchymal stem cell-derived exosomes improved septic lung injury by reducing excessive NETs formation and alleviating inflammatory response.

Abstract

To illustrate the potential of mesenchymal stem cell-derived exosomes (MSC-Exos) in mitigating septic lung injury by reducing the excessive formation of neutrophil extracellular traps (NETs), a mouse model of septic lung injury was induced through cecal ligation and puncture (CLP). The mice received intraperitoneal injections of MSC-Exos. Post injection, pathological alterations of the lung tissue were evaluated through HE staining, and the levels of inflammatory markers in each mouse group at various time points were assessed using ELISA kits. The presence of NETs markers in lung tissue (colocalization of CitH3 and MPO) was determined via immunofluorescence, and the levels of dsDNA in mouse serum were measured using a dsDNA kit. The findings indicated noticeable damage in the sepsis group postsurgically, whereas the severity of lung tissue damage was significantly diminished in mice of the MSC-Exos group. By the 72-h mark after the CLP procedure, there was an elevation in TNF-α, IL-6, IL-1β, and IL-10. Compared to the CLP group, the inflammatory factors in the serum of mice from the CLP + MSC-Exo group were higher at 12 and 24 h but decreased at the 72-h point. Furthermore, the fluorescence intensity of CitH3 and MPO and the dsDNA content increased in the CLP group mice over different time intervals, with MSC-Exos reversing these changes. In summary, MSC-Exos effectively suppressed sepsis-induced NETs formation and ameliorated lung injury.