Melatonin pretreatment can improve the therapeutic effect of Adipose-derived Stem Cells on CCl4-induced liver fibrosis

Abstract Background and Purpose In this study, the therapeutic effect of Mel-incubated ADSCs on CCl 4 -induced hepatic fibrosis was investigated. Methods The experiment was arranged into ADSCS group, ADSCS + Mel group, Model group and Control group with 10 mice in each group. The other three groups of mice were intraperitoneally injected with 8% CCl 4 , and the control group was injected with the same dose of PBS twice a week for 4 weeks. From the fifth week, ADSCs group and ADSCs + Mel group mice were injected with 1×10 6 cells/1 ml PBS dose of ADSCs and 50 μM Mel pretreated ADSCs into tail vein, respectively, twice a week for 2 weeks, and mice in the control and model groups were injected with the same dose of PBS. Samples were tested after six weeks. Results In model group, severe histomathological changes were observed in liver, including severe vacuolation, nuclear fragmentation and liver fibrosis, and these changes were ameliorated by Mel pretreated ADSCs. At the same time, RT-qPCR results showed that Mel-induced ADSCs significantly inhibited the expression of pro-apoptotic genes (Caspase-8, Bax and Caspase-3), and promoted the expression of anti-apoptotic gene (Bcl-2). Immunohistochemical results showed that a large number of MMP-9, TGF-β, MMP-2 yellow-stained positive cells were found in the liver tissues of the model group, while the expression of positive cells was blocked by Mel-induced ADSCs. Conclusion and Implications ADSCs pretreated with Mel significantly improved CCl 4 -induced liver fibrosis, which provides a reference for clinical treatment of liver injury with mesenchymal stem cells.