Human umbilical cord-derived mesenchymal stem cells ameliorate non-alcoholic fatty liver disease via activating TFEB-mediated autophagy in male mice

作者：Huina Zhang, Peng Liu, Yaxuan Deng, Li Wu, Orion Fan, Yanling Cui, Chunxue Zhang, Wenmin Zhu, Yi Sun, Chuwen Lin, Congrong Wang · 发表于：Stem Cell Research & Therapy · 年份：2025 · DOI：10.1186/s13287-025-04855-9 · 被引用次数：1 · 研究领域：Mesenchymal stem cell research、Autophagy in Disease and Therapy、Liver Disease Diagnosis and Treatment

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is characterized by abnormal lipid accumulation in hepatocytes and defective autophagy has been implicated in its pathogenesis. Human umbilical cord-derived MSCs (hUC-MSCs) have shown therapeutic potential in treating NAFLD, while underlying molecular mechanisms remained largely unknown. METHODS: Male C57BL/6J mice fed a choline-deficient high fat diet (CD-HFD) and HepG2 cells exposed to palmitic acid/oleic acid were established as in vivo and in vitro models of NAFLD, respectively. Both models were subjected to treatment with human umbilical cord-derived MSCs (hUC-MSCs). Lipid content, proinflammatory cytokines, fibrosis markers and the hepatic transcriptome were assessed to determine the effect of hUC-MSCs. RESULTS: Here, hUC-MSCs decreased hepatic lipid content and alanine aminotransferase/aspartate aminotransferase levels, as well as attenuated inflammation and fibrosis in choline-deficient high-fat diet (CD-HFD)-induced NAFLD mice. Mechanistically, hUC-MSCs restored impaired autophagic flux and mitigated liver steatosis through the AMPK-mTOR-TFEB pathway in both NAFLD mice and oleic acid/palmitic acid-induced "fatty" HepG2 cells. Of note, hUC-MSCs have been found to promote nuclear translocation of TFEB in PA/OA-induced HepG2 cells. Additionally, TFEB knockdown partially attenuated the effect of hUC-MSCs on enhancing autophagy and lipid metabolism in vitro. CONCLUSIONS: This study suggests that hUC-MSCs represent a po...