A dynamic microphysiological liver model designed for predictive drug metabolism, hepatotoxicity screening, drug-induced liver injury (DILI) assessment, and liver disease modeling under physiologically relevant flow conditions.
- Overview
- Details
- Advantages
- FAQs
Overview
As the central hub for systemic metabolism and detoxification, the liver is highly vulnerable to chemical stress, making drug-induced liver injury (DILI) a leading cause of clinical attrition in drug development. Accurate prediction of hepatic responses requires in vitro models that maintain robust enzymatic activity, complex cellular cross-talk, and physiological hemodynamics over extended periods.
However, primary hepatocytes rapidly lose their metabolic competence (such as CYP450 expression) in conventional static 2D cultures. Liver-on-Chip addresses this limitation by providing a perfusable, microfluidic environment that preserves long-term hepatocyte functionality and supports the co-culture of non-parenchymal cells, enabling more reliable evaluation of metabolic profiles, toxicity, and liver pathologies.
What Is Liver-on-Chip?
Liver-on-Chip is a microfluidic cell culture device designed to recreate the functional architecture of the hepatic microenvironment. By culturing hepatocytes—often alongside non-parenchymal cells like Kupffer cells, hepatic stellate cells, and liver sinusoidal endothelial cells (LSECs)—under controlled fluid flow, the platform maintains prolonged metabolic activity and cellular polarity.
This chip-based liver model can support the study of:
- Prolonged hepatic metabolic competence and CYP450 activity
- Drug metabolism, clearance, and pharmacokinetic (PK) profiling
- Drug-induced liver injury (DILI) and mechanistic hepatotoxicity
- Complex liver diseases such as NAFLD, NASH, and liver fibrosis
- Hepatobiliary transporter function and biliary efflux
- Real-time imaging and continuous sampling for biomarker detection
Fig. 1. Schematics of the development and application of LOC (Liu J, Du Y, et al.,
2024).
Our Liver-on-Chip Platform
Our Liver-on-Chip platform provides a dynamic hepatic model for studying drug metabolism, hepatotoxicity, and complex liver diseases under controlled perfusion.
Key Features
- Prolonged functionality: Maintains stable CYP450 activity and hepatocyte phenotype for extended periods.
- Multicellular co-culture: Supports integration of hepatocytes, Kupffer cells, stellate cells, and LSECs.
- Dynamic perfusion: Mimics hepatic blood flow and physiological shear stress.
- Flexible cell options: Compatible with primary human hepatocytes (PHHs), HepaRG, and iPSC-derived cells.
- Continuous sampling: Enables real-time collection of effluents for metabolite and biomarker detection.
Validation & Readouts
- Hepatic function: Albumin secretion, Urea production, and CYP450 activity assays.
- Toxicity markers: LDH, AST, ALT release, and ROS detection.
- Disease biomarkers: Inflammatory cytokines (e.g., IL-6, TNF-α) and fibrotic markers (e.g., α-SMA, Collagen).
- Downstream analysis: High-content imaging, qPCR, RNA-seq, ELISA, and LC-MS/MS.
Applications
- Hepatotoxicity & DILI: Predict acute, chronic, and immune-mediated drug-induced liver injury.
- Drug Metabolism (DMPK): Evaluate compound clearance, metabolites, and drug-drug interactions.
- Liver Disease Modeling: Build in vitro models of Steatosis, NAFLD, NASH, and liver fibrosis.
- Gene Therapy & Biologics: Assess hepatic uptake and safety of LNPs, AAV vectors, and RNA therapeutics.
FAQs
Q: What cell types are recommended for Liver-on-Chip?
Primary human hepatocytes (PHHs) are the gold standard for metabolism and toxicity studies. However, the platform also supports HepaRG cells, iPSC-derived hepatocytes, and co-cultures with Kupffer cells, hepatic stellate cells, and LSECs depending on the study goals.
Q: Can the chip maintain stable CYP450 activity?
Yes. The dynamic perfusion and 3D-like microenvironment of the Liver-on-Chip help preserve hepatocyte phenotype and CYP450 enzyme activity for weeks, making it ideal for chronic toxicity and repeated dosing studies.
Q: Can Liver-on-Chip be used for DILI testing?
Yes. It is highly predictive for drug-induced liver injury (DILI). By integrating Kupffer cells, the model can also detect immune-mediated hepatotoxicity, which is a major limitation of hepatocyte-only models.
Q: Can it model NASH or liver fibrosis?
Yes. By exposing a co-culture of hepatocytes, stellate cells, and Kupffer cells to free fatty acids (FFAs) or inflammatory stimuli, the platform can successfully model lipid accumulation, inflammation, and fibrotic progression.
Q: What readouts are compatible with this model?
You can perform live-cell imaging, measure secreted biomarkers (Albumin, Urea, LDH, AST/ALT, cytokines) from the effluent, assess CYP450 activity via luminescent assays, and collect cells for qPCR or RNA-seq.
Accelerate your drug discovery and hepatotoxicity assessment with our highly predictive Liver-on-Chip platform.
Contact us today to request product details, pricing, or customized solutions for your liver research.
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