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Human liver organoids for disease modeling of fibrolamellar carcinoma

Nicole J C Narayan, David Requena, Gadi Lalazar, Lavoisier Ramos-Espiritu, Denise Ng, Solomon Levin, Bassem Shebl, Ruisi Wang, William J Hammond, James A Saltsman 3rd, Helmuth Gehart, Michael S Torbenson, Hans Clevers, Michael P LaQuaglia, Sanford M Simon

Published: 9 August 2022

Summary

Fibrolamellar carcinoma (FLC) is a rare, often lethal, liver cancer affecting adolescents and young adults, for which there are no approved therapeutics. The development of therapeutics is hampered by a lack of in vitro models. Organoids have shown utility as a model system for studying many diseases. In this study, tumor tissue and the adjacent non-tumor liver were obtained at the time of surgery. The tissue was dissociated and grown as organoids. We developed 21 patient-derived organoid lines: 12 from metastases, three from the liver tumor and six from adjacent non-tumor liver. These patient-derived FLC organoids recapitulate the histologic morphology, immunohistochemistry, and transcriptome of the patient tumor. Patient-derived FLC organoids were used in a preliminary high-throughput drug screen to show proof of concept for the identification of therapeutics. This model system has the potential to improve our understanding of this rare cancer and holds significant promise for drug testing and development.

Full Access Link: Stem Cell Reports