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

Abstract

This study tested the hypothesis that healthy adipose-derived mesenchymal stem cell (ADMSC)-derived exosomes (HMSC^EXO) and apoptotic (A) (induced by 12 h hypoxia/12 h starvation)-ADMSC-derived exosomes (AMSC^EXO) 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^EXO (100 µg intravenous administration 3 h after CLP), and AMSC^EXO. By day 5 after CLP procedure, the mortality rate was significantly higher in SS than in SC and HMSC^EXO (all P < 0.01), but it showed no significant different between SC and HMSC^EXO, between AMSC^EXO and HMSC^EXO or between SS and AMSC^EXO (P > 0.05). The levels of inflammatory mediators in circulation (CD11^b/c/Ly6G/MIF), bronchioalveolar lavage (CD11^b/c/Ly6G) and abdominal ascites (CD11^b/c/CD14/Ly6G/MIF) were highest in SS, lowest in SC and significantly higher in AMSC^EXO than in HMSC^EXO (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^EXO might be superior to AMSC^EXO for improving survival and suppressing the inflammatory reactions in rats after SS.