InSphero AG has launched a new service, 3D InSight™ Mitochondrial Toxicity Testing, for the identification of mitochondrial liabilities during drug development and safety testing. Data characterizing the mitotoxicity assay was presented Tuesday at EUROTOX 2016, the 52nd Congress of the European Societies of Toxicology. Mitochondrial toxicity is a major adverse mechanism of toxicity for many drugs assigned black box warnings.
When cells encounter stress, such as exposure to toxic drugs, they utilize reserve respiration capacities, which are quantified in the assay as spare respiratory capacity (SRC). A decrease in SRC is one of the first detected consequences of mitochondrial impairment, and the assay compares dose-dependent changes in SRC and cellular viability to assess the likelihood a drug will impair mitochondrial function.
The new service combines the organotypic liver functionality and 28-day in vitro lifespan of 3D InSight™ Human Liver Microtissues with analysis of mitochondrial respiration using the Agilent XFe96 Analyzer. The long-term metabolic competence of 3D liver microtissues enables flexible drug exposures of up to 14 days, while the XFe96 Analyzer allows assessment of mitochondrial function through sensitive and precise measurement of cellular oxygen consumption rate (OCR) on a single microtissue level.
Dr. Jens M. Kelm, InSphero Chief Technology Officer and Co-founder, says the service capitalizes on the in vivo-like biology of 3D human liver microtissues. Kelm says, “Mitochondrial SRC serves as the cell’s energy safety net, a reserve that helps cells respond to stress. When grown in 3D, primary human liver cells have a 4-times greater SRC than when grown in 2D. Using 3D microtissues in the assay not only enables us to expose primary human liver cells to drugs for up to 14 days, but also to measure the drug’s impact on mitochondria in a model that more accurately reflects the cellular response to stress in vivo. By comparing the cellular viability to the mitochondrial function after drug treatment, we can determine if mitochondrial impairment is more likely the primary mechanism of toxicity, or rather a secondary effect.”
A tutorial featuring the 3D InSight™ Mitochondrial Toxicity Service is scheduled to appear in the September 15th issue of Genetic Engineering and Biotechnology News (GEN). It is the latest addition to InSphero’s suite of 3D InSight™ In Vitro Toxicology Services, utilized by the world’s largest pharmaceutical and chemical companies to evaluate drug safety.