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Updated: Aug 11, 2026
Protocol for Isolation of Primary Human Hepatocytes and Corresponding Major Populations of Non-parenchymal Liver Cells
Published on: March 30, 2016
In vitro models to study hepatotoxicity
David A Groneberg1, Christian Grosse-Siestrup, Axel Fischer
1Department of Pediatric Pneumology and Immunology, Charité School of Medicine, Humboldt-University Berlin, Germany. david.groneberg@charite.de
Abstract:
Drug discovery and development consists of a series of processes starting with the demonstration of pharmacological effects in experimental cell and animal models and ending with drug safety and efficacy studies in patients. A main limitation is often the unacceptable level of toxicity with the liver as the primary target organ. Therefore, approaches to study hepatic toxicity in the early phase of drug discovery represent an important step towards rational drug development. A variety of in vitro liver models have been developed in the past years. Next to their use in drug development, they can also be applied to study environmental toxins and their hepatotoxicity. The 3 main approaches are ex vivo isolated and perfused organ models, precision-cut liver slices and cell culture models. Although the advantage of whole organ perfusions is based on the assessment of physiologic parameters such as bile production and morphologic parameters such as tissue histology, cell culture models can be efficiently used to assess cellular metabolism, cytotoxicity and genotoxicity. The advantage of precision-cut liver slices is based on the juxtaposition of cellular assays and tissue morphology. None of these models can be compared as they all focus on different fields of hepatoxicology. For the future, the ideal setup for testing the hepatic toxicity of a new compound could of primary studies in cell or slice cultures to assess cellular effects and secondary studies using ex vivo perfused organs to examine gross organ function parameters and histology.
Insights
Early detection of drug-induced liver toxicity is crucial. This study reviews in vitro liver models, including cell cultures, liver slices, and perfused organs, to assess compound safety during drug discovery.
Area of Science:
- Hepatotoxicology
- Drug Discovery and Development
- In Vitro Toxicology
Background:
- Drug development faces challenges with liver toxicity, a common limitation.
- Early assessment of hepatic toxicity is vital for rational drug design.
- Various in vitro liver models aid in evaluating drug and environmental toxin hepatotoxicity.
Purpose of the Study:
- To review and compare different in vitro liver models for assessing hepatotoxicity.
- To highlight the utility of these models in the early stages of drug discovery.
- To discuss the strengths and limitations of ex vivo perfused organs, liver slices, and cell cultures.
Main Methods:
- Review of established in vitro liver models: ex vivo isolated and perfused organs, precision-cut liver slices, and cell culture models.
- Analysis of the specific applications and parameters assessed by each model type.
- Discussion of how these models contribute to understanding cellular metabolism, cytotoxicity, genotoxicity, and organ function.
Main Results:
- Cell culture models excel at assessing cellular metabolism, cytotoxicity, and genotoxicity.
- Ex vivo perfused organ models provide insights into physiological parameters like bile production and histological integrity.
- Precision-cut liver slices offer a balance, enabling both cellular assays and tissue morphology assessment.
Conclusions:
- No single in vitro liver model is superior; each serves distinct toxicological assessments.
- A tiered approach combining cell/slice cultures for cellular effects and perfused organs for gross function is proposed for future toxicity testing.
- These models are essential for advancing drug safety and understanding environmental toxin effects.
