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A new gold standard for assessing human-relevant liver toxicity
The Liver-Chip is a BioKit Model that Emulate has internally developed and validated. It is available as a BioKit, which includes pre-qualified cells, Organ-Chip consumables, and validated protocols, with guarantees on characterization and functionality.
A new gold standard for assessing human-relevant liver toxicity
The Liver-Chip is a BioKit Model that Emulate has internally developed and validated. It is available as a BioKit, which includes pre-qualified cells, Organ-Chip consumables, and validated protocols, with guarantees on characterization and functionality.
The Emulate human Liver-Chip faithfully recapitulates in vivo physiological functions of the human liver through critical microenvironment features such as 3D multicellular architecture and vascular flow. These features enable the Emulate human Liver-Chip to provide a more human-relevant model of the liver compared to conventional sandwich cultures, spheroids, and animal models, each of which lack relevant features to appropriately model the human liver.
| Category | Feature | Liver-Chip | Sandwich Cultures | Spheroids | Animal Models |
|---|---|---|---|---|---|
| Human Relevance | Human Cells | Yes | Yes | Yes | No |
| Physiologically Relevant Biomarkers & Morphology | +++ | + | + | ++ | |
| Accurate Prediction of Human Hepatotoxicity | +++ | – | ++ | + | |
| Microenvironment | Multi-cellular Complexity | ++ | + | + | +++ |
| Vascular / Media Flow | Yes | No | No | Yes | |
| Tissue-specific ECM | Yes | No | No | Yes | |
| Experimental Deisgn | Tunable Dosing Parameters | ++ | ++ | ++ | + |
| Duration of Experiment | ++ | – | ++ | +++ | |
| Clinically Relevant Assays | +++ | + | + | ++ | |
| Convenience | Speed to Insight | ++ | +++ | +++ | + |
| Ease of Learning Curve | ++ | +++ | +++ | + | |
| Cost-effectiveness | ++ | +++ | +++ | + |
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.
In a landmark study in Communications Medicine, part of Nature Portfolio, researchers demonstrated that the Emulate human Liver-Chip could improve patient safety and reduce small-molecule clinical trial failures due to liver toxicity by up to 87%, with 100% specificity. The Emulate human Liver-Chip enables researchers to assess diverse mechanisms of toxicity with greater fidelity than animal testing or conventional cell culture, lowering the risk of DILI and clinical trial attrition for drug candidates.
Concentration-dependent decrease in mitochondria (yellow) in response to treatment with sitaxsentan at 0, 1, 10, and 100 times the unbound human Cmax for 7 days in the Emulate Liver-Chip S1.
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.
With the Emulate human 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.
AAV Transduction of Hepatocytes in the Emulate human Liver-Chip S1
