Liver Organoids: From Disease Modelling to Regenerative Medicine

Abstract

ABSTRACT Liver organoids are three‐dimensional miniature liver models that recapitulate the complex architecture and key functions of the human liver in vitro, offering powerful platforms for both fundamental research and translational applications. This review systematically summarises current fabrication strategies, disease‐modelling 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‐culture 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‐derived organoids, with no off‐target effects detected at the genome‐wide level. In disease modelling, iPSC‐derived liver organoids faithfully recapitulate the pathological progression of metabolic dysfunction‐associated steatotic liver disease (MASLD) and verify the lipid‐lowering efficacy of semaglutide. Macrophage‐integrated organoid models support the full life cycles of HEV, SARS‐CoV‐2 and dengue virus, providing new tools for antiviral drug screening. Large‐scale patient‐derived tumour organoid biobanks successfully preserve the heterogeneity and clinical drug‐resistance 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‐edited 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.