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Updated: Sep 13, 2025
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Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
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A high-throughput microphysiological system to quantify key events leading to liver fibrosis
Saskia Schmidt1, Laura Suter-Dick2
1School of Life Sciences, University of Applied Sciences and Arts Northwestern Switzerland, Muttenz CH-4132, Switzerland; Department of Pharmaceutical Sciences, University of Basel, Basel CH-4001, Switzerland.
Toxicology
|August 3, 2025
Summary
This study presents a new in vitro liver fibrosis model using microphysiological systems (MPS) to mimic key events of liver fibrosis Adverse Outcome Pathways (AOPs) and reduce animal testing.
Area of Science:
- Toxicology and pharmacology
- In vitro modeling
- Hepatotoxicity research
Background:
- New Approach Methodologies (NAMs) and microphysiological systems (MPS) offer alternatives to animal testing for liver toxicity.
- Standardized in vitro models are needed to study liver fibrosis progression and Adverse Outcome Pathways (AOPs).
Purpose of the Study:
- To develop and validate a scalable, high-throughput in vitro model for liver fibrosis using the Akura™ Twin microplate.
- To mimic key events of the liver fibrosis AOP, including hepatocellular injury and extracellular matrix remodeling.
Main Methods:
- Utilized a 384-well Akura™ Twin microplate with interconnected well pairs for co-culturing HepaRG, THP-1, and hepatic stellate cells (hTERT-HSCs).
- Monitored cell health and metabolic activity using glucose and lactate sensors.
- Assessed hepatocellular injury and fibrosis markers via gene and protein expression analysis following treatment with TGF-β1, MTX, and APAP.
Main Results:
- Hepatocellular injury was indicated by reduced albumin production upon TGF-β1, MTX, and APAP treatment.
- TGF-β1 activated THP-1 cells and increased fibrosis markers (ACTA2, COL1A1, COL3A1, FN1) and extracellular matrix remodeling in hTERT-HSCs.
- The model successfully mimicked key events of the liver fibrosis AOP, with elevated PAI-1 and Pro-Collagen 1A1.
Conclusions:
- The Akura™ Twin platform provides a high-throughput MPS for modeling liver fibrosis.
- This model aids in investigating fibrosis mechanisms and advancing quantitative AOP development as an alternative to animal testing.
