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Generation and characterization of mature hepatocyte organoids for liver metabolic studies

  1. Author:
    Liu, Yuchen [ORCID]
    Zhou, Yaxing
    Ahodantin, James
    Jin, Yu
    Zhu, Juanjuan
    Sun,David
    Wu,Xiaolin
    Su, Lishan
    Yang, Yingzi [ORCID]

  2. Author Address

    Department of Developmental Biology, Harvard School of Dental Medicine, 188 Longwood Ave. Boston, MA 02115, USA., Division of Virology, Pathogenesis, and Cancer, Institute of Human Virology, Departments of Pharmacology and Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA., Cancer Research Technology Program, Frederick National Laboratory for Cancer, Leidos Biomedical Research, Inc., Frederick, MD, 21702, USA., Harvard Stem Cell Institute, Dana-Farber/Harvard Cancer Center, 188 Longwood Ave. Boston, MA 02115, USA., Program in Gastrointestinal Malignancies, Dana-Farber/Harvard Cancer Center, 188 Longwood Ave. Boston, MA 02115, USA.,
    1. Year: 2024
    2. Date: May 15
    3. Epub Date: 2024 05 03
  2. Journal: Journal of Cell Science
    1. 137
    2. 10
  4. Type of Article: Article
  5. Article Number: jcs261961
  1. Abstract:

    Hepatocyte organoids (HOs) generated in vitro recently are powerful tools for liver regeneration. However, the reported HOs were mostly fetal in nature with low expression levels of metabolic genes characteristic of adult liver functions, hampering their application in studying metabolic regulations and therapeutic testing for liver disorders. We report development of novel culture conditions that contains optimized levels of Triiodothyronine (T3) with the removal of growth factors, enabled successful generation of mature hepatocyte organoids (MHOs) with metabolic functions characteristic of adult livers of both mouse and human origins. We showed that the MHOs can be used to study various metabolic functions including bile and urea production, zonal metabolic gene expression, and metabolic alterations in both alcoholic and non-alcoholic fatty liver diseases as well hepatocyte proliferation, injury, and cell fate changes. Notably, the MHOs derived from human fetal hepatoblasts also showed improved hepatitis B virus (HBV) infection. Therefore, these MHOs provide a powerful in vitro model for studies of human liver physiology and diseases. The human MHOs are potentially a robust research tools for therapeutic development as well. © 2024. Published by The Company of Biologists Ltd.

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External Sources

  1. View Full Text
  2. DOI: 10.1242/jcs.261961
  3. PMID: 38700490
  4. PMCID: PMC11166457
  5. View record in Web of Science®
  6. WOS: 001266940200003
  7. PII : 347130

Library Notes

  1. Fiscal Year: FY2023-2024
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