Grants and Contributions:

Grant or Award spanning more than one fiscal year (2017-2018 to 2018-2019).

As a world leader in the field of toxicology, Charles River Laboratories (CRL) is seeking to expand itsx000D
portfolio of toxicology expertises through the development of novel cell-based assays. In this project, wex000D
propose to apply electric cell impedance sensing (ECIS) for the evaluation of functional end-point associatedx000D
with two critical parameters of homeostasis, that is endothelium permeability and platelet aggregation.x000D
Endothelial cells and platelets play pivotal roles in homeostasis and thrombosis and it has become clear thatx000D
vascular safety of drugs constitutes an important criterion in both the drug development and the drug approvalx000D
processes. Drug-induced endothelium leakage is routinely tested in animal models by measuring Evans Bluex000D
endothelium extravasation in organs. Platelet function can be evaluated ex vivo using light transmissionx000D
aggregation assay or by impedance aggregometry which measure platelet adhesion on a pair of electrodex000D
immersed in a whole blood sample. Although very simple and sensitive, theses two standardised in vivox000D
procedures are very low throughput in nature, which makes them rapidly unpractical and expensive if one aimsx000D
at establishing dose-toxicity curves early in the selection of promising lead candidates from compoundx000D
libraries. To address this limitation, we will validate two cell-based assays using an electrical impedancex000D
technology in 96-well format to quantify drugs-induced endothelium permeability and platelet aggregation.