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Cell sources for in vitro human liver cell culture models
Open accessAbstract
In vitro liver cell culture models are gaining increasing importance in pharmacological and toxicological research. The source of cells used is critical for the relevance and the predictive value of such models. Primary human hepatocytes (PHH) are currently considered to be the gold standard for hepatic in vitro culture models, since they directly reflect the specific metabolism and functionality of the human liver; however, the scarcity and difficult logistics of PHH have driven researchers to explore alternative cell sources, including liver cell lines and pluripotent stem cells. Liver cell lines generated from hepatomas or by genetic manipulation are widely used due to their good availability, but they are generally altered in certain metabolic functions. For the past few years, adult and pluripotent stem cells have been attracting increasing attention, due their ability to proliferate and to differentiate into hepatocyte-like cells in vitro. However, controlling the differentiation of these cells is still a challenge. This review gives an overview of the major human cell sources under investigation for in vitro liver cell culture models, including primary human liver cells, liver cell lines, and stem cells. The promises and challenges of different cell types are discussed with a focus on the complex 2D and 3D culture approaches under investigation for improving liver cell functionality in vitro. Finally, the specific application options of individual cell sources in pharmacological research or disease modeling are described.
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“The most commonly applied ECM components for hepatocyte cultures are collagen type I and Matrigel, a commercially available BM matrix extract from Engelbreth-Holm-Swarm (EHS) mouse sarcoma (Serna-Márquez et al., 2020[35]; Zeilinger et al., 2016[49]).”
From Optimization of extracellular matrix for primary human hepatocyte cultures using mixed collagen-matrigel matrices (2023) · cites this paper as Zeilinger et al., 2016[49]
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Metadata
- Authors
- Zeilinger, K., Freyer, N., Damm, G., Seehofer, D., & Knöspel, F.
- Affiliations
- Berlin-Brandenburger Centrum für Regenerative Therapien (DE)
- Stiftung Charité (DE)
- Corresponding author
- Zeilinger, Katrin
- Venue
- Experimental Biology and Medicine
- Publisher
- Frontiers Media SA
- Published
- 2016-07-24
- Volume
- 241
- Issue
- 15
- Pages
- 1684-1698
- ISSN
- 0071-3384 (ISSN-L)
- 1535-3702
- 1535-3699
- PMC
- PMC4999620
- OpenAlex
- W2473248288
- Cited by
- 230
- References
- 158
- Citations by year
- 2026: 15 · 2025: 23 · 2024: 24 · 2023: 29 · 2022: 36 · 2021: 39 · 2020: 25 · 2019: 20 · 2018: 14 · 2017: 5
- FWCI
- 16.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Experimental Biology and Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bundesministerium für Bildung und Forschung (0315741)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- primary human hepatocytes, liver cell lines, pluripotent stem cells, hepatocyte-like cells, monolayer culture, hepatocyte differentiation, disease modeling, drug metabolism, toxicology
- MeSH terms
- Cell Line, Cells, Cultured, Humans, Liver, Stem Cells, Cell Culture Techniques, Hepatocytes, In Vitro Techniques
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