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Human umbilical cord-derived MSCs (hUC-MSCs) have shown therapeutic potential in treating NAFLD, while underlying molecular mechanisms remained largely unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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 \u201cfatty\u201d 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study suggests that hUC-MSCs represent a potential therapeutic approach to treating NAFLD through activating TFEB-mediated autophagy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13287-025-04855-9","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T08:35:22Z","timestamp":1765614922000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Human umbilical cord-derived mesenchymal stem cells ameliorate non-alcoholic fatty liver disease via activating TFEB-mediated autophagy in male mice"],"prefix":"10.1186","volume":"17","author":[{"given":"Huina","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxuan","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orion","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenmin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi Eve","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuwen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8645-1114","authenticated-orcid":false,"given":"Congrong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,13]]},"reference":[{"issue":"9","key":"4855_CR1","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1016\/S2468-1253(22)00165-0","volume":"7","author":"K Riazi","year":"2022","unstructured":"Riazi K, Azhari H, Charette JH, Underwood FE, King JA, et al. 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The experimental protocol received approval from the Ethics Committee of Shanghai East Hospital (Approved project: Preparation and banking of clinical-grade human umbilical cord and cord blood stem cells, Approval No. Tilinshen-2017-001, Date of approval: Dec 15, 2017). Umbilical cord guardians provided written informed consent for the use of samples. All relevant procedures involving animal experiments were approved by the Animal Welfare Ethics Committee of Shanghai Sixth People\u2019s Hospital Affiliated with Shanghai Jiao Tong University School of Medicine (Approved project: Human umbilical cord-derived mesenchymal stem cells ameliorate non-alcoholic fatty liver disease via activating TFEB-mediated autophagy, Approval No. DWLL2019-0026, Date of approval: Sep 20, 2024).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"34"}}