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

Cell sources for in vitro human liver cell culture models

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

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1177/1535370216657448

Cites

158 of 158 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The most commonly applied ECM components for hepatocyte cultures are collagen type I and Matrigel.

    “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]

    The “2D and 3D culture models for PHH” section identifies rat-tail collagen and Matrigel as ECM components used in hepatocyte sandwich cultures. It does not establish that they are the most commonly applied components across hepatocyte cultures generally. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 4

  1. [26]26. Jiang J, Wolters JE, van Breda SG, Kleinjans JC, de Kok TM. Development of novel tools for the in vitro investigation of druginduced liver injury. Expert Opin Drug Metab Toxicol 2015; 11 :1523-37
  2. [82]82. Darnell M, Schreiter T, Zeilinger K, Urbaniak T, So ¨ derdahl T, Rossberg I, Dillne ´r B, Berg AL, Gerlach JC, Andersson TB. Cytochrome P450dependent metabolism in HepaRG cells cultured in a dynamic threedimensional bioreactor. Drug Metab Dispos 2011; 39 :1131-8
  3. [111]111. Cai J, DeLaForest A, Fisher J, Urick A, Wagner T, Twaroski K, Cayo M, Nagaoka M, Duncan SA. Protocol for directed differentiation of human pluripotent stem cells toward a hepatocyte fate. StemBook [Internet]. Cambridge, MA: Harvard Stem Cell Institute, 2012
  4. [131]131. Sancho-Bru P, Roelandt P, Narain N, Pauwelyn K, Notelaers T, Shimizu T, Ott M, Verfaillie C. Directed differentiation of murineinduced pluripotent stemcells to functional hepatocyte-like cells. J Hepatol 2011; 54 :98-107

Cited by

Sorted by citations

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
Published
2016-07-24
Volume
241
Issue
15
Pages
1684-1698
ISSN
  • 0071-3384 (ISSN-L)
  • 1535-3702
  • 1535-3699
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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review