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Updated: May 5, 2026
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Protocol for Isolation of Primary Human Hepatocytes and Corresponding Major Populations of Non-parenchymal Liver Cells
Published on: March 30, 2016
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In vitro liver models for toxicological research.
Ichiro Fukunaga1, Takanori Takebe2
1Center for Genomic and Regenerative Medicine, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8431, Japan.
Drug Metabolism and Pharmacokinetics
|April 9, 2025
Summary
Drug-induced liver injury (DILI) research is shifting towards advanced 3D liver organoids. These models offer a more human-relevant alternative to animal testing for toxicology assessments.
Area of Science:
- Toxicology
- Biotechnology
- Hepatology
Background:
- Drug-induced liver injury (DILI) poses significant challenges in drug development and chemical safety.
- Rodent models are standard for preclinical toxicology but raise ethical concerns and lack human-specific ADME profiling.
- Existing in vitro models like primary and immortal hepatocytes have limitations.
Purpose of the Study:
- To review 3D liver organoid models as alternatives for DILI testing.
- To explore cell sources, bioengineering methods, and assay design for in vitro toxicology.
- To guide the development of context-of-use assays for novel methods.
Main Methods:
- Review of current literature on 3D liver organoid models.
- Analysis of various cell sources, including stem cell-derived hepatocytes.
- Discussion of bioengineering techniques and relevant biomarkers for toxicology.
Main Results:
- 3D liver organoids show promise as a more human-relevant in vitro model for DILI.
- Integration of diverse cell sources and culture methods is key for robust assays.
- Selection of appropriate training compounds and biomarkers is critical for assay validation.
Conclusions:
- 3D liver organoids represent a significant advancement in alternative methods for DILI assessment.
- Optimizing cell sources and bioengineering is essential for reliable in vitro toxicology.
- This review provides a framework for designing rational in vitro toxicology testing strategies.
