Stem Cells From Human Exfoliated Deciduous Teeth Attenuated Mice Autoimmune Hepatitis

Background and objective:Autoimmune hepatitis(AIH)is an immune-mediated liver inflammatory disease that can be present in acute or chronic forms.AIH has a variety of clinical manifestations,including occult onset without any symptoms,acute onset and even acute liver failure.At present,the main clinical treatment of AIH is glucocorticoid alone or combined with immunosuppressive azathioprine,which requires long-term use of drugs,and is prone to cause side effects,and the complete remission rate is low.Therefore,it is urgent to explore new effective treatment strategy for AIH.Stem cells from human exfoliated deciduous tooth(SHED)are abundant in tissue source,easy to obtain,non-invasive and have low immune rejection.Variety of animal experiments and clinical studies have demonstrated that SHED had a good therapeutic effect on autoimmune diseases.In this study,SHED was used to intervene in mice with autoimmune hepatitis induced by concanavalin A(Con A)and to evaluate their therapeutic effect.Methods: SHED was cultured in vitro and its proliferation capacity and multi-lineage differentiation ability were assessed.Fifteen female C57BL/6 mices were randomly divided into three groups: control group(Control),autoimmune hepatitis group(Con A)and treatment group(SHED+Con A).After 24 h of Con A induction,the liver tissues and peripheral blood of each group were collected.The levels of TNF-α and IFN-γ cytokines in peripheral blood of mice were measured by ELISA,and peripheral blood ALT and AST were detected.Perform a liver Knodell score.The isolated liver tissue was histologically analyzed by HE staining and immunohistochemical staining.Results: 1.SHED have rapid proliferation ability,and both alizarin red staining and oil red O staining are positive.2.The serum ALT,AST and Knodell scores of Con A group were significantly higher than those of the Control group and the SHED+Con A group was significantly lower than the Con A group.3.The expression levels of inflammatory factors TNF-α and IFN-γ in serum and liver tissues of Con A group were significantly higher than those of Control group,and the SHED+Con A group was lower than the Con A group.4.The expression levels of CD3+ and CD4+ T cells in the liver tissue of the Con A group were significantly higher than those in the Control group,and the SHED+Con A group was significantly lower than the Con A group.5.The expression level of NF-κB in liver tissue of Con A group was significantly higher than that of Control group,and SHED+Con A group was significantly lower than the Con A group.Conclusion: 1.SHED showed capacity of proliferation,adipogenic and osteoplastic differentiation.2.SHED showed therapeutic effect on Con A-induced autoimmune hepatitis in mice.3.SHED inhibited the activation of CD3+ and CD4+ T cells in the liver,reduced the secretion of inflammatory factors TNF-α and IFN-γ by Th1 cells,and alleviated liver damage.4.SHED inhibited the expression of inflammatory factors TNF-α and IFN-γ by blocking NF-κB signaling pathway.