We are proud to announce the publication of the largest in vitro benchmarking study on hepatotoxicity assessment, in Toxicological Sciences, the official journal of the Society of Toxicology. This research, conducted together with scientists from FDA’s National Center for Toxicological Research (NCTR), demonstrates how 3D human liver microtissues could reduce the reliance on animal models and 2D cell culture, providing more predictive, scalable, and high-throughput solutions for drug safety testing.
Industry-ready Liver Microtissues for Hepatotoxicity Assessment
In this study, 152 FDA-approved small molecule drugs were tested using 3D InSight™ Human Liver Microtissues, InSphero’s microphysiological hepatic model composed of primary parenchymal and non-parenchymal liver cells. These microtissues, cultivated in the scalable 384-well Akura™ Spheroid Microplates, offer a highly physiological alternative to the traditional 2D culture of immortalized liver cell lines traditionally used for hepatotoxicity screens.
Key Highlights of the Peer-reviewed Paper
- The study tested 152 FDA-approved drugs (Figure 1) and demonstrated that 3D liver microtissues accurately predict drug-induced liver injury (DILI), one of the leading causes of drug development discontinuation.
- A rigorous statistical analysis, featuring a large, diverse, and balanced drug set, combined with stringent 5-fold cross-validation, ensured the robustness and relevance of the results.
- The results, achieved by the scientists from InSphero and FDA’s NCTR are compelling: the applied 3D in vitro liver model correctly flagged 80% of the withdrawn drugs due to liver toxicity, while it accurately classified 89% of the safe drugs. For liver-toxic drugs targeting the nervous system, the liver microtissues achieved a 90% success rate.
- The use of 384-well Akura™ Spheroid Microplates enables high-throughput screening, making the system scalable and ideal for large-scale hepatotoxicity assessment applications.
- This study not only marks a significant advancement in early liver toxicity detection, but it also highlights the unmatched predictive power of the 3D liver microtissue technology. InSphero’s Liver Safety Platform's showcased promising path to reducing late-stage drug failures and has the potential to save millions in R&D costs and accelerate the development of safer drugs.
