Early prediction of drug-induced toxicity is critical to prevent liabilities being detected at a late stage when considerable time and expense has been invested in a project. Following a number of well publicised drug withdrawals from the market due to toxicity, the industry is now keen to adopt approaches which ensure any potential adverse effects are detected at an early stage. However, developing assays which can accurately predict human toxicity can be challenging, especially in the case of idiosyncratic toxicity which only manifests itself in a small percentage of the population.
Human cell-based models tend to be the most popular for assessing drug-induced toxicity in vitro. These assays have the advantage of being of human origin and allow specific mechanisms of toxicity to be explored. Through the advent of stem cells and 3D cell models, coupled with sophisticated confocal imaging technology, more complex models can be developed and analysed. The longevity of these models allows for repeat dose regimens to be tested, and the models more closely represent the cell-cell interactions observed in vivo. For example, the Cyprotex videos below illustrate a spontaneously beating 3D cardiac microtissue developed as a tri-culture model consisting of iPSC-derived cardiomyocytes, cardiac endothelial cells and cardiac fibroblasts, and provide a 360° view of a microtissue spheroid.
A new publication in Drug Discovery World (Spring 2016 edition) titled ‘Microtissues for in vitro toxicity assessment: Cost effective and in vivo relevant toxicology tools’ has been recently authored by Cyprotex. It provides a review of 3D cell-based assays including a focus on organ-specific cardiac, hepatic and renal models, co-culture models, and how these models can be used to predict different mechanisms of toxicity.