{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:46:47Z","timestamp":1782452807461,"version":"3.54.5"},"reference-count":28,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Animal models have limitations in predicting human clinical outcomes, highlighting the need for advanced human\u2010relevant models. We aimed to establish multilineage human liver organoids (hLOs) for modelling fibrosis and metabolic dysfunction\u2013associated steatotic liver disease (MASLD), and for evaluating pharmacological and genetic interventions<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>hLOs were generated from human induced pluripotent stem cells by stepwise co\u2010differentiation. Fibrosis was induced by transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2), and steatotic injury by free fatty acids. Hydronidone and resmetirom were used for pharmacological studies. Lentiviral knockdown of YB1 in hepatocytes and STAT3 in hepatic stellate cells was used for lineage\u2010restricted genetic perturbation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TGF\u2010\u03b2 induced a fibrotic phenotype in hLOs, with stellate cell activation, increased extracellular matrix secretion, and Sirius Red\u2013positive matrix deposition. Free fatty acid treatment induced an acute lipotoxic MASLD\u2010like phenotype characterised by steatosis, hepatocyte apoptosis, inflammatory activation, and fibrotic remodelling. Hydronidone attenuated fibrotic responses, whereas resmetirom reduced steatosis, inflammation, hepatocyte injury, and fibrosis\u2010associated changes. In parallel, YB1 knockdown in hepatocytes and STAT3 knockdown in stellate cells ameliorated steatotic and fibrogenic phenotypes, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Multilineage hLOs provide a human\u2010relevant platform for modelling fibrosis and MASLD and for evaluating therapeutic and genetic interventions in a multicellular liver context.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70716","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T09:01:22Z","timestamp":1780304482000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Application of Multilineage Human Liver Organoids in Disease Modelling, Drug Testing and Genetic Intervention"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3412-2033","authenticated-orcid":false,"given":"Qichao","family":"Ge","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Developmental and Regenerative Biology iORGANtech (SuZhou) Limited Company  SuZhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanjing","family":"Zhangdi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuecheng","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangwen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Jian","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Continent Pharmaceuticals Co., Ltd.  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