Applications of organoid technology in basic and translational research on liver diseases

Liver organoids (LOs) are derived from pluripotent stem cells, adult stem cells (ASCs), or primary hepatic tissues using three-dimensional (3D) culture systems. These models self-assemble in vitro and recapitulate key hepatic structures and functions, thereby creating complementary platforms for liver development studies, as well as research on disease pathogenesis, drug metabolism/toxicity, and translational applications. The continuous improvement in engineering technologies has permitted LOs and liver-on-a-chip platforms to be applied to a variety of liver diseases such as fatty liver disease, inherited liver disorders, drug-induced liver injury (DILI), fibrotic liver disease, and hepatocellular carcinoma. Nevertheless, the widening deployment of LOs is impeded by numerous source-specific limitations. Although pluripotent stem cell-derived LOs are often immature, fetal-like, and lineage-biased, tissue-derived LOs continue to be hampered by limited sample availability, donor-to-donor variability, expansion-related phenotypic drift, and challenges in their standardization. Incomplete recapitulation of the native microenvironment, as well as high cross-batch variability, continues to hinder clinical translation in both systems.