Precision-cut human liver slice cultures as an immunological platform
Open accessAbstract
The liver is the central metabolic organ in the human body, and also plays an essential role in innate and adaptive immunity. While mouse models offer significant insights into immune-inflammatory liver disease, human immunology differs in important respects. It is not easy to address those differences experimentally. Therefore, to improve the understanding of human liver immunobiology and pathology, we have established precision-cut human liver slices to study innate immunity in human tissue. Human liver slices collected from resected livers could be maintained in ex vivo culture over a two-week period. Although an acute inflammatory response accompanied by signs of tissue repair was observed in liver tissue following slicing, the expression of many immune genes stabilized after day 4 and remained stable until day 15. Remarkably, histological evidence of pre-existing liver diseases was preserved in the slices for up to 7 days. Following 7 days of culture, exposure of liver slices to the toll-like receptor (TLR) ligands, TLR3 ligand Poly-I:C and TLR4 ligand LPS, resulted in a robust activation of acute inflammation and cytokine genes. Moreover, Poly-I:C treatment induced a marked antiviral response including increases of interferons IFNB, IL-28B and a group of interferon-stimulated genes. Therefore, precision-cut liver slices emerge as a valuable tool to study human innate immunity.
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Induction of MASLD in vitro using FFAs leads to pronounced and quantitatively measurable lipid accumulation in cell lines within 24-72 h, contrasting with animal models where HFD induces steatosis in 8-16 weeks, steatohepatitis in 16-36 weeks, and fibrosis/cirrhosis in 24-52 weeks or more.
“Induction of MASLD in vitro using free fatty acids leads to a pronounced and quantitatively measurable accumulation of lipids in cell lines within 24–72 h [29].”
From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [59]
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Bioengineered Liver Models for Investigating Disease Pathogenesis and Regenerative Medicine
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Self-citationThe HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease
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Experimental Models for Studying Structural and Functional State of the Pathological Liver (Review)
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Human Liver Slices to Investigate Injury and Repair
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- Authors
- Wu, X., Roberto, J. B., Knupp, A., Kenerson, H. L., Truong, C. D., Yuen, S. Y., Brempelis, K. J., Tuefferd, M., Chen, A., Horton, H., Yeung, R. S., & Crispe, I. N.
- Affiliations
- University of Washington (US)
- Janssen (Belgium) (BE)
- Corresponding author
- Wu, Xia
- ORCID
- Venue
- Journal of Immunological Methods
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 455
- Pages
- 71-79
- ISSN
- 0022-1759 (ISSN-L)
- PMC
- PMC6689534
- OpenAlex
- W2790293777
- Cited by
- 81
- References
- 50
- Citations by year
- 2026: 13 · 2025: 6 · 2024: 7 · 2023: 6 · 2022: 10 · 2021: 14 · 2020: 12 · 2019: 9 · 2018: 4
- FWCI
- 4.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Immunological Methods (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Washington
- Janssen Research and Development
- Seattle Foundation
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- precision-cut liver slices, human liver, innate immunity, Toll-like receptor activation, poly(I:C), lipopolysaccharide, interferon response, interferon-stimulated genes, liver inflammation, cytokine expression
- MeSH terms
- Interferon Lambda, Gene Expression Regulation, Humans, Immunity, Innate, Inflammation, Interferons, Interleukins, Lipopolysaccharides, Liver, Organ Culture Techniques, Poly I-C, Interferon-beta, Cell Culture Techniques, Toll-Like Receptor 3, Toll-Like Receptor 4
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.
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