Validation of cell impedance sensing as a high-throughput approach for toxicity evaluation in vitro

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As a world leader in the field of toxicology, Charles River Laboratories (CRL) is seeking to expand itsportfolio of toxicology expertises through the development of novel cell-based assays. In this project, wepropose to apply electric cell impedance sensing (ECIS) for the evaluation of functional end-point associatedwith two critical parameters of homeostasis, that is endothelium permeability and platelet aggregation.Endothelial cells and platelets play pivotal roles in homeostasis and thrombosis and it has become clear thatvascular safety of drugs constitutes an important criterion in both the drug development and the drug approvalprocesses. Drug-induced endothelium leakage is routinely tested in animal models by measuring Evans Blueendothelium extravasation in organs. Platelet function can be evaluated ex vivo using light transmissionaggregation assay or by impedance aggregometry which measure platelet adhesion on a pair of electrodeimmersed in a whole blood sample. Although very simple and sensitive, theses two standardised in vivoprocedures are very low throughput in nature, which makes them rapidly unpractical and expensive if one aimsat establishing dose-toxicity curves early in the selection of promising lead candidates from compoundlibraries. To address this limitation, we will validate two cell-based assays using an electrical impedancetechnology in 96-well format to quantify drugs-induced endothelium permeability and platelet aggregation.