Summary
Published in Toxicology in Vitro (2024), this peer-reviewed study used 3D Petri Dish® micro-molds to form scaffold-free 3D microtissues. Full citation: Bronsard, J., et al. 3D multi-cell-type liver organoids: A new model of non-alcoholic fatty liver disease for drug safety assessments
3D multi-cell-type liver organoids: A new model of non-alcoholic fatty liver disease for drug safety assessments
Research Overview
Liver organoids are useful for drug discovery and toxicology, but two limitations hold them back: weak expression and activity of xenobiotic-metabolizing enzymes, and difficulty modeling non-alcoholic fatty liver disease, which itself alters those enzymes.
This study generated 3D multi-cell-type liver organoids — ‘HML organoids’ — from HepaRG cells, primary human macrophages, and hepatic-stellate-derived LX-2 cells. The team also developed a fatty liver disease model by culturing the organoids for nine days under disease-inducing conditions, producing a system that pairs metabolic competence with a disease phenotype for toxicity assessment.
Key Discoveries
- HML organoids combine HepaRG hepatocytes, primary human macrophages, and stellate-derived LX-2 cells
- Addresses the weak xenobiotic-metabolizing enzyme activity of conventional liver organoids
- A 9-day culture protocol produced a non-alcoholic fatty liver disease model in the same system