InSphero 3D Liver Microtissues Featured at Annual SOT Meeting
Product News Mar 31, 2017
InSphero 3D InSight™ Human Liver Microtissues were identified as a more sensitive, highly specific in vitro model for predicting drug induced liver injury (DILI) and investigating mechanisms of drug toxicity in a series of presentations at the Society of Toxicology’s 56th Annual Meeting (SOT), held in Baltimore, Maryland, March 12-16. InSphero produces 3D liver microtissues using its patent-pending 3D Select™ Process, which yields standardized 3D models that are pre-validated and certified for use in industry-scale in vitro safety and efficacy testing applications.
During the SOT 3D Cell Platforms to Advance Toxicology Sciences workshop, Dr. William Proctor, Head of Investigative Toxicology at Genentech, presented data from an intensive validation study conducted by Genentech and AstraZeneca. The study revealed InSphero Human Liver Microtissues provide twice the sensitivity as traditional primary human hepatocyte (PHH) assays in predicting toxicity of clinically known DILI drugs. Dr. Proctor cited a specific case study in which a blinded compound had shown elevated liver enzymes in Phase I clinical trials in patients. The compound had escaped detection by traditional in vitro screens, but was detected by InSphero 3D InSight™ microtissues at concentrations that reflected clinically relevant dosing levels. Dr. Proctor indicated the model has been instituted in the Genentech group as a secondary (Tier 2) DILI screen.
Commenting on the presentation, InSphero Chief Executive Officer and Co-founder Dr. Jan Lichtenberg, says, ”This study provides convincing evidence that InSphero liver microtissues deliver higher sensitivity without sacrificing specificity. Having two of the world’s leading pharmaceutical companies produce this collaborative, thorough validation further confirms that our 3D models not only reflect in vivo biology, but also deliver the reproducibility and scalability required to meet the early stage screening demands of large pharma. Our assay-ready 3D InSight™ models offer a cost-effective, turn-key solution that gives toxicologists greater confidence when characterizing risk in lead compound sets.”
Additional SOT presentations highlighted the InSphero suite of human and animal-derived liver microtissues for investigative toxicology applications. A novel assay for detecting mitochondrial toxicity was described in collaborative work with Agilent Technologies. Using the Seahorse XFe96 Analyzer to monitor mitochondrial respiration, InSphero 3D InSight™ Human Liver Microtissues displayed a 6-fold increase in spare respiratory capacity compared to 2D PHH, thus providing a significantly larger assay window for detection and classification of mitochondrial liabilities. Oral and poster presentations described the advantages of InSphero rat, monkey, and dog liver microtissues for cross-species analysis of DILI and in vitro mechanistic toxicity studies to reduce the need for costly and ethically charged animal studies.