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Updated: Mar 8, 2026
Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
Characterization of rat or human hepatocytes cultured in microphysiological systems (MPS) to identify hepatotoxicity
Shih-Yu Chang1, Jenna L Voellinger2, Kirk P Van Ness2
1Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.
Abstract:
The liver is the main site for drug and xenobiotics metabolism, including inactivation or bioactivation. In order to improve the predictability of drug safety and efficacy in clinical development, and to facilitate the evaluation of the potential human health effects from exposure to environmental contaminants, there is a critical need to accurately model human organ systems such as the liver in vitro. We are developing a microphysiological system (MPS) based on a new commercial microfluidic platform (Nortis, Inc.) that can utilize primary liver cells from multiple species (e.g., rat and human). Compared to conventional monolayer cell culture, which typically survives for 5-7days or less, primary rat or human hepatocytes in an MPS exhibited higher viability and improved hepatic functions, such as albumin production, expression of hepatocyte marker HNF4α and canaliculi structure, for up to 14days. Additionally, induction of Cytochrome P450 (CYP) 1A and 3A4 in cryopreserved human hepatocytes was observed in the MPS. The acute cytotoxicity of the potent hepatotoxic and hepatocarcinogen, aflatoxin B1, was evaluated in human hepatocytes cultured in an MPS, demonstrating the utility of this model for acute hepatotoxicity assessment. These results indicate that MPS-cultured hepatocytes provide a promising approach for evaluating chemical toxicity in vitro.
Insights
A novel microphysiological system (MPS) using liver cells shows improved viability and function for up to 14 days. This advanced liver model aids in assessing drug safety and environmental contaminant toxicity.
Area of Science:
- Hepatology
- Toxicology
- Biotechnology
Background:
- The liver is crucial for drug and xenobiotic metabolism.
- Accurate in vitro liver models are needed for drug development and environmental health assessments.
- Current cell culture methods have limited viability and functionality.
Purpose of the Study:
- To develop and validate a microphysiological system (MPS) for modeling human liver function.
- To assess the utility of the MPS for evaluating drug toxicity and environmental contaminant effects.
Main Methods:
- Utilized a commercial microfluidic platform (Nortis, Inc.) with primary rat and human hepatocytes.
- Cultured hepatocytes in the MPS for up to 14 days, comparing to conventional monolayer cultures.
- Assessed hepatocyte viability, albumin production, HNF4α expression, canaliculi structure, CYP induction, and aflatoxin B1 cytotoxicity.
Main Results:
- Hepatocytes in MPS showed higher viability and improved hepatic functions for up to 14 days compared to monolayer cultures.
- Observed induction of Cytochrome P450 (CYP) 1A and 3A4 in human hepatocytes within the MPS.
- Demonstrated the MPS's utility for assessing acute hepatotoxicity using aflatoxin B1.
Conclusions:
- MPS-cultured hepatocytes offer enhanced viability and sustained liver functions in vitro.
- The MPS provides a promising platform for in vitro chemical toxicity and hepatotoxicity assessments.
- This model can improve the predictability of drug safety and efficacy in clinical development.
