Cited by 230Drug-Induced Hepatotoxicity and ProtectionLiver physiology and pathology3D Printing in Biomedical Research

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Cell sources for in vitro human liver cell culture models

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Zeilinger, Katrin, Freyer, Nora, Damm, Georg, Seehofer, Daniel, Knöspel, Fanny·2016·Experimental Biology and Medicine

DOI 10.1177/1535370216657448PMC PMC4999620

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Abstract

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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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
ORCID: Zeilinger, Katrin
Damm, Georg
Seehofer, Daniel
Knöspel, Fanny
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
DOI: 10.1177/1535370216657448
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
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
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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Cell sources for in vitro human liver cell culture models

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