{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:36:31Z","timestamp":1791549391950,"version":"4.3.4"},"reference-count":99,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81460202"],"award-info":[{"award-number":["81460202"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Liver organoids are three\u2010dimensional miniature liver models that recapitulate the complex architecture and key functions of the human liver in\u00a0vitro, offering powerful platforms for both fundamental research and translational applications. This review systematically summarises current fabrication strategies, disease\u2010modelling utilities and regenerative potentials of liver organoids, alongside the major challenges and future directions. In recent years, the field has witnessed several breakthroughs. Through endothelial co\u2010culture approaches, vascularised and metabolically zonated liver organoids have been successfully generated, achieving endothelial coverage exceeding 85%. Prime editing enables precise correction of pathogenic mutations in patient\u2010derived organoids, with no off\u2010target effects detected at the genome\u2010wide level. In disease modelling, iPSC\u2010derived liver organoids faithfully recapitulate the pathological progression of metabolic dysfunction\u2010associated steatotic liver disease (MASLD) and verify the lipid\u2010lowering efficacy of semaglutide. Macrophage\u2010integrated organoid models support the full life cycles of HEV, SARS\u2010CoV\u20102 and dengue virus, providing new tools for antiviral drug screening. Large\u2010scale patient\u2010derived tumour organoid biobanks successfully preserve the heterogeneity and clinical drug\u2010resistance signatures of liver cancers. In regenerative medicine, encapsulated hepatocyte organoids and the UTOpiA bioartificial liver system have effectively rescued acute liver failure in animal models, while gene\u2010edited autologous organoids offer potential curative strategies for genetic disorders such as Wilson disease. Nevertheless, insufficient hepatocyte functional maturity, difficulties in constructing vascular networks, and the lack of standardised culture protocols remain major obstacles to clinical translation. By bridging fundamental liver biology and clinical practice, liver organoid technology lays a solid foundation for precision hepatology and regenerative therapies. Continued interdisciplinary efforts are still required to overcome current limitations and facilitate its clinical adoption.<\/jats:p>","DOI":"10.1111\/cpr.70268","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T12:59:26Z","timestamp":1786712366000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Liver Organoids: From Disease Modelling to Regenerative Medicine"],"prefix":"10.1111","author":[{"given":"Tiepeng","family":"Wang","sequence":"first","affiliation":[{"name":"Xinjiang Second Medical College  Karamay Xinjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotian","family":"Qu","sequence":"additional","affiliation":[{"name":"Xinjiang Second Medical College  Karamay Xinjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhong","family":"Si","sequence":"additional","affiliation":[{"name":"Xinjiang Second Medical College  Karamay Xinjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4854-2027","authenticated-orcid":false,"given":"Junkang","family":"Meng","sequence":"additional","affiliation":[{"name":"Carver College of Medicine, the University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine, Shihezi University  Shihezi Xinjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuliang","family":"Niu","sequence":"additional","affiliation":[{"name":"Xinjiang Second Medical College  Karamay Xinjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"issue":"6","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1016\/j.jhep.2022.08.021","article-title":"Global Burden of Primary Liver Cancer in 2020 and Predictions to 2040","volume":"77","author":"Rumgay H.","year":"2022","journal-title":"Journal of Hepatology"},{"issue":"5","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.jhep.2023.01.025","article-title":"Utilization of Livers Donated After Circulatory Death for Transplantation\u2014An International Comparison","volume":"78","author":"Eden J.","year":"2023","journal-title":"Journal of Hepatology"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/s41573-025-01317-y","article-title":"Human Organoids as 3D In\u00a0Vitro Platforms for Drug Discovery: Opportunities and Challenges","volume":"25","author":"Wang D.","year":"2025","journal-title":"Nature Reviews Drug Discovery"},{"issue":"10","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1038\/s41580-020-0259-3","article-title":"Human Organoids: Model Systems for Human Biology and Medicine","volume":"21","author":"Kim J.","year":"2020","journal-title":"Nature Reviews Molecular Cell Biology"},{"issue":"7244","key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/nature07935","article-title":"Single Lgr5 Stem Cells Build Crypt\u2010Villus Structures In\u00a0Vitro Without a Mesenchymal Niche","volume":"459","author":"Sato T.","year":"2009","journal-title":"Nature"},{"issue":"7436","key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nature11826","article-title":"In Vitro Expansion of Single Lgr5+ Liver Stem Cells Induced by Wnt\u2010Driven Regeneration","volume":"494","author":"Huch M.","year":"2013","journal-title":"Nature"},{"issue":"1","key":"e_1_2_11_8_1","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.cell.2014.11.050","article-title":"Long\u2010Term Culture of Genome\u2010Stable Bipotent Stem Cells From Adult Human Liver","volume":"160","author":"Huch M.","year":"2015","journal-title":"Cell"},{"issue":"9","key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1038\/nprot.2016.097","article-title":"Culture and Establishment of Self\u2010Renewing Human and Mouse Adult Liver and Pancreas 3D Organoids and Their Genetic Manipulation","volume":"11","author":"Broutier L.","year":"2016","journal-title":"Nature Protocols"},{"issue":"6","key":"e_1_2_11_10_1","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/j.cell.2018.11.012","article-title":"Inflammatory Cytokine TNF\u03b1 Promotes the Long\u2010Term Expansion of Primary Hepatocytes in 3D Culture","volume":"175","author":"Peng W. 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