Abstract
BACKGROUND: Autoimmune hepatitis is a serious autoimmune liver disease that threatens human health worldwide, which emphasizes the urgent need to identify novel treatments. Stem cells from human exfoliated deciduous teeth (SHED), which are easy to obtain in a non-invasive manner, show pronounced proliferative and immunomodulatory capacities. AIM: To investigate the protective effects of SHED on concanavalin A (ConA)-induced hepatitis in mice, and to elucidate the associated regulatory mechanisms. METHODS: We used a ConA-induced acute hepatitis mouse model and an in vitro co-culture system to study the protective effects of SHED on ConA-induced autoimmune hepatitis, as well as the associated underlying mechanisms. RESULTS: SHED infusion could prevent aberrant histopathological liver architecture caused by ConA-induced infiltration of CD3(+), CD4(+), tumor necrosis-alpha(+), and interferon-gamma(+) inflammatory cells. Alanine aminotransferase and aspartate aminotransferase were significantly elevated in hepatitis mice. SHED infusion could therefore block ConA-induced alanine aminotransferase and aspartate aminotransferase elevations. Mechanistically, ConA upregulated tumor necrosis-alpha and interferon-gamma expression, which was activated by the nuclear factor-kappa B pathway to induce hepatocyte apoptosis, resulting in acute liver injury. SHED administration protected hepatocytes from ConA-induced apoptosis. CONCLUSION: SHED alleviates ConA-induced acute liver injury via inhibition of hepatocyte apoptosis mediated by the nuclear factor-kappa B pathway. Our findings could provide a potential treatment strategy for hepatitis.