Investigate mechanisms of toxicity for preclinical drug candidates to help decrease clinical trial safety failures
Drug-induced liver injury (DILI) is a primary concern during drug development that remains poorly understood due to species differences in liver toxicity and the limited predictivity of conventional in vitro models. The quad-culture Emulate Liver-Chip combines four human cell types in a dynamic microenvironment to support in vivo like gene expression, functionality, and physiology. Applications include general and mechanistic toxicity evaluation, as well as biomarker identification and mechanism of action determination.
A validated and comprehensive preclinical human liver model
The human Liver-Chip supports relevant aspects of the liver microenvironment through 3D multicellular architecture, physical forces such as flow, and liver-specific physiological function. Conventional sandwich cultures lack endothelium and mechanical forces while organoids lack relevant tissue-tissue interfaces and cytoarchitecture critical for reliable in vivo-to-in vitro correlations.
Reduce clinical translation issues
Rat and dog models only predict 71% of drug toxicities in humans according to one study. The Liver-Chip is human-based, helping researchers reduce clinical translation issues caused by species differences.
Contains key hepatic cell types
Tissue complexity is crucial for hepatic phenotypes and not typical of conventional cell culture. The Liver-Chip includes primary hepatocytes, stellate cells, Kupffer cells, and liver sinosoidal endothelial cells to capture complex cell-cell interactions.
Physiologically relevant morphology
Hepatocytes in the Liver-Chip form branched bile canalicular networks lined by functional MRP2 efflux transporters, while conventional hepatocyte sandwich cultures fail to form and maintain characteristic liver morphology.
Enhanced in vivo-like function
Unlike static hepatocyte sandwich monocultures, albumin and urea secretion is comparable to in vivo ranges and is maintained over time, indicating enhanced functionality.
Drug-induced liver injury remains a primary cause of drug candidate attrition and withdrawal from the market
Current preclinical models inadequately predict hepatotoxicity and DILI in humans. Poor clinical translation arises from species differences present in animal models and the limited in vivo-relevant physiology of conventional liver cell culture. This not only leads to high preclinical and clinical attrition, but also can pose serious health risks to patients.
A more predictive in vitro model of human hepatotoxicity
The Emulate Liver-Chip enables researchers to assess preclinical safety with greater fidelity than animal testing or conventional cell culture, allowing for the de-risking of drug candidates to reduce the risk of DILI and clinical trial attrition. Companion studies with species-specific animal cells on-chip can also be performed to enable in vivo-in vitro translation. Diverse mechanisms of hepatotoxicity can be investigated with the Liver-Chip, including:
- Hepatocellular injury
- Kupffer cell depletion
Part of the Human Emulation System®
The Human Emulation System is comprised of instruments, consumables, and software in a flexible, open format. The user-friendly platform gives researchers a window into the inner workings of human biology.
Technical Note: Development and Characterization of the Species-Specific Liver-Chip
Learn how the Liver-Chip can be applied to emulate the complex functions and physiology of the human liver.