organ-Chips

Liver-Chip

Assess toxicity and vector efficiency for preclinical drug candidates with Organ-on-a-Chip technology to accelerate therapeutic development 

Liver‑Chip Overview

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 assessment of AAV-based gene therapy transduction efficiency and safety. 

Characterization

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 functions. 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.

Model complex cell-cell interactions

Tissue complexity is crucial for hepatic phenotypes but is not typical of conventional cell culture. The Liver-Chip includes primary hepatocytes, stellate cells, Kupffer cells, and liver sinusoidal 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.  

Capture in vivo like expression

Unlike static hepatocyte sandwich monocultures, albumin and urea secretion is comparable to in vivo ranges and is maintained over time, indicating enhanced functionality.

Application: Hepatotoxicity

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 it can also pose serious health risks to patients. 

Benefits

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, lowering the risk of DILI and clinical trial attrition for drug candidates. 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
  • Steatosis
  • Cholestasis
  • Kupffer cell depletion

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Application: AAV TRANSDUCTION 

Development of safe and efficient gene therapy vectors remains slow

Gene therapy holds enormous promise for inherited and acquired genetic diseases, yet progress remains slow. Developing safe and effective viral vectors is time consuming and challenging. Animal studies are slow, costly, and tightly regulated, while conventional in vitro models’ limited cellular complexity results in non-physiological response. These challenges have led not only to a slow pace of gene therapy approval, but also serious safety risks to patients. 

AAV Transduction of Hepatocytes in the Liver-Chip

Benefits

A faster path to AAV optimization

With the Liver-Chip, researchers can test the delivery efficiency and safety of adeno-associated virus (AAV) vectors in a human-relevant model of the liver sinusoid and get results in weeks—not months, like with animal models. With this application, it is possible to rapidly iterate on AAV design and explore each cell type’s contribution, accelerating optimization ahead of clinical trials.

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.

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Bio-Kit

Includes chips, reagents, and pre-qualfieid pre-qualified human cells.

Services

Standard services and custom collaboration projects available.

Basic Kit

Includes chips and reagents for use with customer cell sourcing.

FEATURED RESOURCE

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.