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

作者:Chang, Chia Lo; Sung, Pei Hsun; Chen, Kuan Hung; Shao, Pei Lin; Yang, Chih Chao; Cheng, Ben Chung; Lin, Kun Chen; Chen, Chih Hung; Chai, Han Tan; Chang, Hsueh Wen; Yip, Hon Kan; Chen, Hong Hwa*
来源:American Journal of Translational Research, 2018, 10(4): 1053-1070.

摘要

This study tested the hypothesis that healthy adipose-derived mesenchymal stem cell (ADMSC)-derived exosomes (HMSCEXO) 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 HMSCEXO (100 mu g 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 HMSCEXO (all P < 0.01), but it showed no significant different between SC and HMSCEXO. between AMSC(EXO) and HMSCEXO 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 HMSCEXO (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-alpha/NF-kappa B/IL-1 beta) 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, HMSCEXO might be superior to AMSC(EXO) for improving survival and suppressing the inflammatory reactions in rats after SS.