Cited by 61Liver physiology and pathologyPluripotent Stem Cells ResearchTissue Engineering and Regenerative Medicine

Human liver organoids: From generation to applications

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Afonso, Marta B., Marques, Vanda, van Mil, Saskia W.C., Rodrigues, Cecilia M.P.·2024·Hepatology

Abstract

In the last decade, research into human hepatology has been revolutionized by the development of mini human livers in a dish. These liver organoids are formed by self-organizing stem cells and resemble their native counterparts in cellular content, multicellular architecture, and functional features. Liver organoids can be derived from the liver tissue or pluripotent stem cells generated from a skin biopsy, blood cells, or renal epithelial cells present in urine. With the development of liver organoids, a large part of previous hurdles in modeling the human liver is likely to be solved, enabling possibilities to better model liver disease, improve (personalized) drug testing, and advance bioengineering options. In this review, we address strategies to generate and use organoids in human liver disease modeling, followed by a discussion of their potential application in drug development and therapeutics, as well as their strengths and limitations.

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  • 3D liver organoid systems better preserve cell identity and enable longer-term propagation compared with traditional 2D models while also supporting patient-specific disease modeling and drug testing.

    “Among the most impactful advances has been the rise of 3D liver organoid systems, which better preserve cell identity and enable longer-term propagation compared with traditional 2D models while also supporting patient-specific disease modeling and drug testing approaches [40,41].”

    From The Hepatocyte Expansion Paradox: A Review of In Vitro Challenges and Advances (2026) · cites this paper as [41]

    The Introduction says 3D cultures better resemble liver tissue than 2D cultures, and the Liver Disease Modeling and Drug Discovery sections describe patient-derived organoids that retain individual genetic backgrounds and support drug testing. The section on organoids derived from primary liver tissue also describes their expansion, but does not establish a general longer-term propagation advantage over 2D models; it reports that adult human hepatocyte organoids deteriorated after 2.5 months. (LLM, conf=0.82)

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Cited by

Sorted by citations

Authors
Afonso, M. B., Marques, V., van Mil, S. W. C., & Rodrigues, C. M. P.
Affiliations
  • University of Lisbon (PT)
  • Center for Molecular Medicine, University Medical Center Utrecht and Utrecht University, The Netherlands
  • Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal
Venue
Hepatology
Published
2023-02-27
Volume
79
Issue
6
Pages
1432-1451
ISSN
0270-9139 (ISSN-L)
OpenAlex
W4321598219
Cited by
61
References
30
Citations by year
2026: 32 · 2025: 21 · 2024: 8
FWCI
2.63
Type
journal article
Language
en
Open access
Locations
  • Hepatology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
Funders
ZonMw (09150181910029)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
liver organoids, organoid formation, pluripotent stem cells, liver disease modeling, drug testing, personalized medicine, bioengineering
MeSH terms
Humans, Liver, Liver Diseases, Organoids, Pluripotent Stem Cells

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