Effects Of Human Adipose Tissue-Derived Stromal Cells On Mutiple Organ Injury Induced By Sepsis Combined With Mechanical Ventilation In Mice

Objectives: Sepsis always leads to lung,liver and kidney failure.Mechanical ventilation(MV)is an essential method to support respiratory failure,but it also can injure the lungs which is called ventilation induced lung injury(VILI).Our study uses the sepsis combined with mechanical ventilation model to simulated the clinical situations.We aim to test the effects of human adipose tissue-derived stromal cells(hADSC)on the sepsis combined with mechanical ventilation induced organ injuries in mice..Materials and methods: Adult male wild type C57 mice were divided into 5 groups: 1)Sham group;2)MV group;3)CLP(cecal ligation and puncture)group;4)CLP+MV group;5)CLP+MV+MSC(mesenchymal stem cells)group.Sepsis in mice was induced by CLP surgery.12 hours after CLP,mice were ventilated at conventional tidal volumes(12 ml/kg),with or without hADSCs at the same time.Survival rates were observed during the first 7 days.The organ function of livers and kidneys were assayed by ALT,AST,BUN and Scr.Tissue injury were detected by HE stain.The production and release of inflammatory cytokines(IL-6,TNF-α)were analyized by q-PCR and ELISA.Alveolar total protein and cells were measured.Results: The survival rates,liver and kidney functions of mice in CLP+MV group had no differences to that of the mice in CLP group.The HE scores of lungs,alveolar total protein increased evidently in the mice of CLP+MV group comparing to the mice of CLP group.The significant increase also could be seen in IL-6 mRNA level of lungs and livers.The IL-6 protein level in serum and bronchoalveolar lavage fluid(BALF)increased obviously too.The liver functions and survival rates of the mice in CLP+MV+MSC group were improved by the hADSCs.hADSCs also obviously decreased the HE scores of lungs,total protein and cells in BALF.The mRNA level of IL-6 and TNF-α in lungs,livers and kidneys,and the protein level of IL-6 in serum and BALF decreased dramatically too.Conclusions: Our study indicates that hADSCs could obviously reduce the mutiple organ injuries induced by sepsis and mechanical ventilation,and increased survival rates,which may provide a new therapy for the sepsis patients who need mechanical ventilation.