Precision-Cut Liver Slices in Hepatic Disease Modeling

Precision-cut liver slices (PCLSs) are thin, uniform sections of hepatic tissue that preserve the native architecture, multicellular composition and cell–matrix interactions of the liver. Prepared from human or animal specimens, PCLSs provide an ex vivo platform in which disease processes—from initial lipid accumulation through inflammation and fibrosis—can be studied in a controlled environment. This model bridges the gap between isolated cell cultures, which lack tissue organisation, and in vivo studies, which can be confounded by systemic variables. PCLSs have been applied to a range of liver disorders, including non-alcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver disease (ALD), viral hepatitis and drug-induced liver injury. In each case, culture conditions are tailored—with defined combinations of sugars, fatty acids, cytokines or toxins—to induce pathophysiological hallmarks such as steatosis, hepatocyte apoptosis, activation of hepatic stellate cells and extracellular matrix deposition. The versatility of PCLSs also allows assessment of therapeutic candidates, mechanistic interrogation by transcriptomic profiling and testing of anti-fibrotic or anti-steatotic compounds. Recent advances in culture media, bioreactor technologies and prolonged incubation protocols have extended tissue viability up to six days, facilitating studies of chronic injury and repair. Overall, PCLSs represent a robust tool for dissecting cellular crosstalk, validating drug targets and predicting clinical responses without the ethical and translational limitations of whole-animal experiments.

Research from Nature Portfolio

Recent studies have demonstrated the value of PCLSs in the preclinical evaluation of antifibrotic therapies. One notable report described the discovery of a small-molecule inhibitor targeting the RNA-binding protein LARP6, a regulator of type I collagen synthesis. Application of this inhibitor to PCLSs prepared from fibrotic human liver markedly reduced collagen secretion, myofibroblast activation and extracellular matrix accumulation ex vivo. When tested in prophylactic and therapeutic animal models of liver fibrosis, the compound prevented fibrosis onset and attenuated disease progression, with minimal off-target gene expression changes. These findings validate PCLSs as an ex vivo bridge to in vivo efficacy studies and highlight the potential of targeted collagen biosynthesis inhibitors in managing hepatic fibrosis.

Precision-Cut Liver Slices in Hepatic Disease Modeling publication trend

The graph below shows the total number of articles in precision-cut liver slices in hepatic disease modeling across all publications each year (not limited to Nature Index journals).

Technical terms

Precision-cut liver slice (PCLS): A thin section of liver tissue maintained ex vivo to preserve three-dimensional architecture and multicellular interactions for disease modelling.

Ex vivo: Experimental studies conducted on tissues or organs outside the living organism, under controlled laboratory conditions.

Steatosis: Accumulation of triglyceride droplets within hepatocytes, an early feature of fatty liver disease.

Fibrosis: Pathological deposition of extracellular matrix proteins, notably collagen, leading to tissue scarring and impaired function.

Hepatic stellate cell: A perisinusoidal liver cell that, upon activation, differentiates into a collagen-producing myofibroblast during fibrogenesis.

Transcriptomics: High-throughput analysis of gene expression patterns, often by RNA sequencing, to elucidate molecular pathways in tissue samples.

References

1. Precision-cut liver slices: a versatile tool to advance liver research. Hepatology International (2018).
2. A Bioreactor Technology for Modeling Fibrosis in Human and Rodent Precision‐Cut Liver Slices. Hepatology (2019).
3. Discovery and evaluation of inhibitor of LARP6 as specific antifibrotic compound. Scientific Reports (2019).
4. Metabolic Dysfunction-Associated Steatotic Liver Disease in a Dish: Human Precision-Cut Liver Slices as a Platform for Drug Screening and Interventions. Nutrients (2024).
5. Human Precision-Cut Liver Slices: A Potential Platform to Study Alcohol-Related Liver Disease. International Journal of Molecular Sciences (2023).
6. A Pathophysiological Model of Non-Alcoholic Fatty Liver Disease Using Precision-Cut Liver Slices. Nutrients (2019).