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; Helmuth Gehart; Michael S. Torbenson; Hans Clevers; Michael P. LaQuaglia; Sanford M. Simon

doi:10.1016/j.stemcr.2022.06.003

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, Helmuth Gehart, Michael S. Torbenson, Hans Clevers, Michael P. LaQuaglia, Sanford M. Simon

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Pages (from-to)	1874-1888
Number of pages	15
Journal	Stem Cell Reports
Volume	17
Issue number	8
DOIs	https://doi.org/10.1016/j.stemcr.2022.06.003
State	Published - Aug 9 2022

Keywords

fibrolamellar
liver cancer
pediatric cancer

ASJC Scopus subject areas

Biochemistry
Genetics
Developmental Biology
Cell Biology

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10.1016/j.stemcr.2022.06.003

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Narayan, N. J. C., Requena, D., Lalazar, G., Ramos-Espiritu, L., Ng, D., Levin, S., Shebl, B., Wang, R., Hammond, W. J., Saltsman, J. A., Gehart, H., Torbenson, M. S., Clevers, H., LaQuaglia, M. P., & Simon, S. M. (2022). Human liver organoids for disease modeling of fibrolamellar carcinoma. Stem Cell Reports, 17(8), 1874-1888. https://doi.org/10.1016/j.stemcr.2022.06.003

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abstract = "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.",

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doi = "10.1016/j.stemcr.2022.06.003",

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AU - Narayan, Nicole J.C.

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AU - Ng, Denise

AU - Levin, Solomon

AU - Shebl, Bassem

AU - Wang, Ruisi

AU - Hammond, William J.

AU - Saltsman, James A.

AU - Gehart, Helmuth

AU - Torbenson, Michael S.

AU - Clevers, Hans

AU - LaQuaglia, Michael P.

AU - Simon, Sanford M.

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N2 - 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.

AB - 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.

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Human liver organoids for disease modeling of fibrolamellar carcinoma

Abstract

Keywords

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