LATE-BREAKING ABSTRACT: Human mesenchymal stem cell exosomes attenuates sepsis-induced acute lung injury via inhibition of oxidative stress and the MAPK-NF-κB pathway

Background and objectives: Acute lung injury (ALI) secondary to sepsis is a complex syndrome associated with high morbidity and mortality. Mesenchymal stem cells (MSCs) or its conditioned medium were demonstrated to reduce alveolar inflammation, improve lung endothelial barrier permeability and modulate the oxidative stress in vivo and in vitro. Recently, MSCs were found to release exosomes that could deliver proteins, bio-active lipids and nucleic acids to injured cells. The current study was designed to determine if exosomes released by MSCs would be effective in sepsis-induced ALI mice and the potential mechanisms. Methods and results: After six hours of cecal ligation and puncture (CLP), mice received saline, exosomes-depleted conditioned media (ExD-CM) or exosomes via the tail vein. Exosomes administration not only improved pulmonary microvascular permeability, but also inhibited histopathological changes and infiltration of polymorphonuclear granulocytes into lung tissues. In addition, activities of anti-oxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase and lipid peroxidation were significantly increased in the exosomes group versus the saline and ExD-CM groups. Furthermore, exosomes suppressed phosphorylation of NF-κB and MAPK and degradation of IκB, an NF-κB inhibitor. Decreased activities of nuclear factor-erythroid-2-related-factor-2 and heme oxygenase-1 caused by sepsis were reversed by exosomes. Conclusions: Those findings suggest that one of the protective mechanisms of exosomes on sepsis-induced ALI is throughupregulation of antioxidative enzymes and inhibition of MAPK-NF-κB activation.