Adipose-derived mesenchymal stem cell-derived exosomes alleviate overwhelming systemic inflammatory reaction and organ damage and improve outcome in rat sepsis syndrome

This study tested the hypothesis that healthy adipose-derived mesenchymal stem cell (ADMSC)-derived exosomes (HMSC ) and apoptotic (A) (induced by 12 h hypoxia/12 h starvation)-ADMSC-derived exosomes (AMSC ) were comparably effective at alleviating sepsis syndrome [SS; induced by cecal-ligation and puncture (CLP)]-induced systemic inflammation and reduced organ damage and unfavorable outcomes in rats. SD rats were divided into sham control (SC), SS only, SS + HMSC (100 µg intravenous administration 3 h after CLP), and AMSC . By day 5 after CLP procedure, the mortality rate was significantly higher in SS than in SC and HMSC (all P < 0.01), but it showed no significant different between SC and HMSC , between AMSC and HMSC or between SS and AMSC (P > 0.05). The levels of inflammatory mediators in circulation (CD11 /Ly6G/MIF), bronchioalveolar lavage (CD11 /Ly6G) and abdominal ascites (CD11 /CD14/Ly6G/MIF) were highest in SS, lowest in SC and significantly higher in AMSC than in HMSC (all P < 0.001). The circulating/splenic levels of immune cells (CD34+/CD4+/CD3+/CD8+) were expressed in an identical pattern whereas the T-reg+ cells exhibited an opposite pattern of inflammation among the groups (all P < 0.001). The protein expressions of inflammation (MMP-9/MIF/TNF-α/NF-κB/IL-1β) and oxidative stress (NOX-1/NOX-2/oxidized protein), and cellular expressions (CD14+/CD68+) in lung/kidney parenchyma exhibited an identical pattern of inflammatory mediators (all P < 0.001). The kidney/lung injury scores displayed an identical pattern of inflammatory mediators among the groups (all P < 0.001). In conclusion, HMSC might be superior to AMSC for improving survival and suppressing the inflammatory reactions in rats after SS.