SHED ameliorated concanavalin A-induced autoimmune hepatitis by protecting hepatocytes from apoptosis

Abstract

Background：Autoimmune hepatitis (AIH) is serious autoimmune liver diseases that threaten people’s health worldwide, emphasizing the need to identify novel treatment. Stem cells from human exfoliated deciduous teeth (SHED), which is easy to obtain and non-invasive, showed pronounced proliferation and immunomodulation capacity. This study aims to investigate the effect of SHED on ConA-induced AIH and the potential underlying mechanisms.Methods: We used a concanavalin A (ConA) induced acute hepatitis mouse model and in vitro co-culture system to study the protective effects of SHED on ConA-induced autoimmune hepatitis and the underlying mechanisms.Results: SHED infusion could prevent aberrant histopathological architecture of liver with infiltration of abundant of CD3+, CD4+, TNF-α+ and IFN-γ+ inflammatory cells induced by ConA. The expression of ALT and AST which indicated the liver function significantly elevated in hepatitis mice. While SHED infusion could block the elevation of ALT and AST induced by ConA. Mechanistically, Con-A upregulated TNF-α and IFN-γ expression activated NF-κB pathways to induced hepatocyte apoptosis, resulting in acute liver injury. SHED administration protected hepatocytes from Con-A-induced apoptosis. Conclusions: These results demonstrated that SHED alleviated ConA-induced acute liver injury via inhibition of hepatocyte apoptosis mediated by the NF-κB pathways. Our findings could provide a potential prevention and therapeutic strategy for hepatitis and acute hepatic injury.