Human liver organoids: From generation to applications
Open accessAbstract
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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Bioinspired Spatially Ordered Multicellular Lobules for Liver Regeneration
Wang, J., Huang, D., Ren, H., & Zhao, Y. (2025) · Research · doi:10.34133/research.0634 · Cited by 10 · see citing works
The Hepatocyte Expansion Paradox: A Review of In Vitro Challenges and Advances
Kolahdouzmohammadi, M., Tjandra, N., Wu, K., Nikoumaram, R., & Oldani, G. (2026) · Cells · doi:10.3390/cells15161465
“…advances has been the rise of 3D liver organoid systems, which better preserve cell identity and enable longer-term propagation compared with traditional https://doi.org/10.3390/cells15161465 2D models while also supporting patient-specific disease modeling and drug testing approaches [40,41].”
Influential
- 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)
- PMC
- PMC11095893
- 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
- hybrid
- doi.org
- Licence
- 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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