S6: Advances in high content imaging in toxicology
Advances in high content imaging in toxicology: 2D and 3D cell based models
Department of Toxicology at Cyprotex Discovery, UK
Senior Research Scientist
High content imaging (HCI) is a powerful tool for cell-based toxicology. Monolayer culture provide rapid and robust models for a wide range of applications including genotoxicity testing, cytotoxicity profiling and detection of detrimental toxicology outcomes. We will discuss current developments in these areas including HCS classification of genotoxins as aneugen or clastogen.
Three-dimensional cell culture models, or microtissues, resemble the complex in vivo environment better than 2D equivalents. Microtissues can be formed from a variety of cell types including primary cells and induced pluripotent stem cells (iPSC). Here we present an overview of microtissue models representing key human organs derived from a co-culture of primary cells and/or combined with iPSC. Human liver microtissue (hLiMT), formed from primary hepatocytes and kupffer cells, can predict the potential for drug-induced liver injury (DILI) using indicators of organoid health including ROS, glutathione content, DNA structure and mitochondrial function. Cardiac models, generated using iPSC derived cardiomyocytes plus primary human endothelial and fibroblast cells in co-culture spontaneous beat following five days in culture. A HCI assay analysing hypertrophy, calcium homeostasis and mitochondrial function was developed. Repeat dosing over 14 days resulted in the correct prediction of 14/14 known structural cardiotoxins.