A sensitive in vitro hepatotoxicity assay that accurately predicts human DILI
DILI remains a major cause of drug attrition, due to the limitations of in vitro hepatotoxicity assays and in vivo models.
Most medications are metabolized in the liver, which makes it one of the primary tissues affected by adverse drug reactions. Earlier identification means that promising drugs can undergo structural modifications to address toxicity issues to lower attrition rates. To do so requires preclinical assays with greater human relevance and sensitivity.
Utilizing our Liver-on-a-chip model, the PhysioMimix DILI Assay allows you to predict human liver responses to acute and chronic drug exposure, in the presence/absence of underlying disease.
This in vitro hepatotoxicity assay consists of human primary liver parenchymal and non-parenchymal cells (NPCs) cultured in 3D under perfusion to form tissues from which it is possible to detect functional liver-specific endpoints (including clinical biomarkers such as albumin and ALT/AST). The assay enables the sensitive assessment of compound toxicity with full dose–response curves and, by incorporating Kupffer cells, allows for the evaluation of immune-mediated toxicity.
Both acute and chronic exposure to compounds can be assessed by comparing responses to single- and multi-dosed tissues for up to four weeks. The assay produces highly functional and metabolically active liver tissues for DILI screens to give deep mechanistic insights into the toxicity profile of a compound.
Limitations with current techniques
- Poor in vitro to in vivo translation
- Fail to provide deep mechanistic insights into the cause of toxicity
- Many advanced in vitro models are low throughput limiting the number of data points
- Challenging to run chronic exposure assays
- Production of toxic phase I and II metabolites is not possible
Advancements with PhysioMimix OOC®
- Translate data from the lab to the clinic by using clinical biomarker reporting
- Assess multiple cellular endpoints to determine the mechanism of toxicity
- Generate full dose–response curves for multiple compounds per plate
- Long-term liver cultures facilitate prolonged repeat dosing for weeks
- Correlate the production of toxic phase I and II metabolites with cell health measurements
Standard DILI cell culture timeline
End point measurements
Longitudinal and endpoint measurements include (but not limited to):
- Cytochrome P450 enzyme activity
- Albumin production
- Urea production
Clinical liver heath biomarkers
- Lactose dehydrogenase (LDH) release
- Adenosine Triphosphate (ATP)
- Aspartate Transferase (AST)/Alanine amino transferase (ALT)
Optional profiling analysis
- Quantitative PCR
Generate high content data for a complete DILI profile
Our sensitive DILI assay provides high-content data from every replicate allowing the exploration of mechanisms of DILI alongside the assessment of a range of cell health markers.
Improve in vitro to in vivo translation
Improved data translatability from the lab to the human is achieved through full dose–response experiments measuring clinical markers, such as ALT/AST, and has been tested using a range of toxic therapeutics.
Access our DILI Service
Get instant access to the PhysioMimix DILI Assay via our CRO Service. Through a collaborative approach, our experts work with you to plan and execute your study.
Standard and bespoke projects are carried out by our dedicated team of scientists in our CRO facility providing you with actionable data within weeks.
Add PhysioMimix OOC into your lab
Harness the power of PhysioMimix OOC in your own lab with the purchase of a single- or multi-organ microphysiological system.
With a growing community of users and support from our experts, there has never been a better time to transition into 3D cell culture.