Human Menstrual Blood-derived Stem Cell Transplantation Suppresses Liver Injury in DDC-induced Chronic Cholestasis
Abstract Background: Cholestasis liver injury can lead to serious symptoms and prognoses in the clinic. Currently, an effective medical treatment is not available for cholestasis liver injury. Human menstrual blood-derived stem cells (MenSCs) have been considered an emerging treatment in various diseases. However, efficiency of MenSCs in cholestasis liver injury has been less investigated. Methods: C57/BL6 mice were fed with 3,5-diethoxycarbonyl-1,4- dihydroxychollidine (DDC) to induce chronic cholestasis liver injury model. DDC mice were injected with either phosphate buffer saline (PBS) or MenSCs at 2 and 4 weeks. Mice were sacrificed at 5 weeks. Serum and liver tissues were collected to test liver function and pathological changes. Proteomics and western blot were used to explore the related molecular mechanisms. Adeno-associated virus (AAV)9 infected mice were used for verifications of MenSC treatment target and related molecular mechanism. Results: We found that MenSCs could protect mice against DDC-induced cholestasis by improving impaired liver function and tissue damage. MenSCs markedly prolonged survival rate of mice, decreased the mice serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), direct bilirubin (DBIL) and total bilirubin (TBIL) levels as well as intrahepatic cholestasis, bile duct dilation and fibrosis. The results further indicated that MenSCs repaired DDC-induced tight junction (TJ) and bile transport function damage and inhibited COL1A1, α-SMA and TGF-β1 activation by upregulating liver β-catenin expression. MenSC transplantation could be an effective treatment method for cholestasis liver injury.