Conditioned secretome of adipose-derived stem cells improves dextran sulfate sodium-induced colitis in mice

摘要

BACKGROUND Inflammatory bowel diseases(IBD)is related to uncontrolled immune response.Currently,there is no successful treatment for significant improvement in IBD.Stem cells display their therapeutic effects through their repopulating capacity or secreting factors.AIM To investigate the effects of conditioned mouse adipose-derived stem cells(mADSCs)secretome on colitis-induced mice.METHODS mADSCs were isolated from adipose tissue of C57BL/6 mice.Conditioned mADSCs secrectome was obtained by culturing of mADSCs with lipopolysaccharides(LPS,1μg/mL)for 24 h.Acute colitis was induced by 2%dextran sulfate sodium(DSS)drinking water for 7 d and then normal drinking water for 4 d.The mice were treated with normal culture medium(NM group),conditioned mADSCs secretome(CM group)or mADSCs(SC group).The length of colon and histopatholgy of colon tissues were evaluated.The mRNA expression levels of inflammatory cytokines in colon tissue and the serum interleukin(IL)-6 levels were determined.RESULTS The isolated mADSCs maintained the mADSCs specific gene expression profiles during experiment.The conditioned mADSCs secretome released by the treatment of mADSCs with LPS contained mainly inflammatory chemokines,colony-stimulating factors and inflammatory cytokines.The loss of body weight and reduction in colon length were ameliorated in the CM group.The conditioned mADSCs secretome reduced the histological score in colon tissue.The expression of IL-1b and IL-6 mRNAs in colon tissues significantly inhibited in the CM group compared to SC group and NM group,respectively.The elevation of serum IL-6 levels was also ameliorated in the CM group.These results indicate that the conditioned mADSCs secretome suppressed the synthesis of inflammatory cytokines in damaged colon tissue and the elevation of serum IL-6 concentration in DSS-induced mice CONCLUSION Conditioned mADSCs secretome might play regenerative roles by the suppression of IL-6 in serum and tissue during acute colitis,and may be more effective than stem cells themselves in the regeneration of colon tissue.