- •Precision-cut liver slices (PCLS) can be used to study hepatocyte-intrinsic regulation of cell death ex vivo.
- •Increased induction of apoptosis is detected in PCLS from adenovirus- and LCMV-infected livers after TNF challenge ex vivo.
- •Optimized protocol may enable the characterization of human hepatocyte sensitivity to apoptosis in PCLS from patients with liver diseases.
Background & Aims
Abbreviations:IP3 (inositol-3-phosphate), LCMV (lymphocytic choriomeningitis virus), PCLS (precision-cut liver slices), PLCg (phospholipase C gamma), ROS (reactive oxygen species), TNF (tumor necrosis factor)
- Godoy P.
- Hewitt N.J.
- Albrecht U.
- Andersen M.E.
- Ansari N.
- Bhattacharya S.
- et al.
Materials and methods
Mouse and human liver
Preparation of PCLS
Improved preparation of mouse and human PCLS
PCLS as ex vivo model system to study hepatocyte sensitivity to apoptosis
Data availability statement
Conflict of interest
- Multimedia component 1
- Multimedia component 2
- Multimedia component 3
- Living in the liver: hepatic infections.Nat Rev Immunol. 2012; 12: 201-213
- Defective T-cell immunity in hepatitis B virus infection: why therapeutic vaccination needs a helping hand.Lancet Gastroenterol Hepatol. 2018; 3: 192-202
- Immune surveillance of the liver by T cells.Sci Immunol. 2020; 5
- Reduced mitochondrial resilience enables non-canonical induction of apoptosis after TNF receptor signaling in virus-infected hepatocytes.J Hepatol. 2020; 73: 1347-1359
- TNF-induced target cell killing by CTL activated through cross-presentation.Cell Rep. 2012; 2: 478-487
- Metabolic zonation of the liver: regulation and implications for liver function.Pharmacol Ther. 1992; 53: 275-354
- Commensal-driven immune zonation of the liver promotes host defence.Nature. 2021; 589: 131-136
- Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME.Arch Toxicol. 2013; 87: 1315-1530
- Optimization and validation of a novel three-dimensional co-culture system in decellularized human liver scaffold for the study of liver fibrosis and cancer.Cancers. 2021; 13: 4936
- Vascularized and functional human liver from an iPSC-derived organ bud transplant.Nature. 2013; 499: 481-484
- Precision-cut liver slices: a versatile tool to advance liver research.Hepatol Int. 2019; 13: 51-57
- Preparation and incubation of precision-cut liver and intestinal slices for application in drug metabolism and toxicity studies.Nat Protoc. 2010; 5: 1540-1551
- Precision-cut human liver slice cultures as an immunological platform.J Immunol Methods. 2018; 455: 71-79
- Precision-cut liver slices as an alternative method for long-term hepatotoxicity studies.Arch Toxicol. 2020; 94: 2889-2891
- Maintenance of drug metabolism and transport functions in human precision-cut liver slices during prolonged incubation for 5 days.Arch Toxicol. 2017; 91: 2079-2092
- Liver slices as a model to study fibrogenesis and test the effects of anti-fibrotic drugs on fibrogenic cells in human liver.Toxicol In Vitro. 2008; 22: 771-778
- Precision-cut tissue slices as a tool to predict metabolism of novel drugs.Expert Opin Drug Metab Toxicol. 2007; 3: 879-898
- Human precision-cut liver slices as an ex vivo model to study idiosyncratic drug-induced liver injury.Chem Res Toxicol. 2013; 26: 710-720
- Human precision-cut liver slices as a model to test antifibrotic drugs in the early onset of liver fibrosis.Toxicol In Vitro. 2016; 35: 77-85
- Fibrogenic cell phenotype modifications during remodelling of normal and pathological human liver in cultured slices.Liver Int. 2010; 30: 1529-1540
- Precision-cut liver slices from diet-induced obese rats exposed to ethanol are susceptible to oxidative stress and increased fatty acid synthesis.Am J Physiol Gastrointest Liver Physiol. 2014; 306: G208-217
- Viral activation of cellular metabolism.Virology. 2015; 479-480: 609-618
- Immunobiology and pathogenesis of hepatitis B virus infection.Nat Rev Immunol. 2021;
- Kupffer cell-dependent hepatitis occurs during influenza infection.Am J Pathol. 2006; 168 (quiz 1404-1165): 1169-1178
- SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19.J Hepatol. 2020; 73: 807-816
- Adaptive immunity: an emerging player in the progression of NAFLD.Nat Rev Gastroenterol Hepatol. 2020; 17: 81-92
- Drug-induced liver injury.Nat Rev Dis Primers. 2019; 5: 58
Author names in bold designate shared co-first authorship.
User licenseCreative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0) |
For non-commercial purposes:
- Read, print & download
- Redistribute or republish the final article
- Text & data mine
- Translate the article (private use only, not for distribution)
- Reuse portions or extracts from the article in other works
- Sell or re-use for commercial purposes
- Distribute translations or adaptations of the article
Elsevier's open access license policy