Reference number : GC-2017-Q4-00691, amendment number : , agreement type : G, recipient legal name : Grandbois, Michel (Université de Sherbrooke), recipient country : CA, recipient province : nan, recipient city : Quebec|Québec, recipient postal code : nan, program name english : Engage Grants for universities, program name french : Subventions d'engagement partenarial pour les universités, program purpose english : As a world leader in the field of toxicology, Charles River Laboratories (CRL) is seeking to expand its_x000D_
portfolio of toxicology expertises through the development of novel cell-based assays. In this project, we_x000D_
propose to apply electric cell impedance sensing (ECIS) for the evaluation of functional end-point associated_x000D_
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 that_x000D_
vascular safety of drugs constitutes an important criterion in both the drug development and the drug approval_x000D_
processes. Drug-induced endothelium leakage is routinely tested in animal models by measuring Evans Blue_x000D_
endothelium extravasation in organs. Platelet function can be evaluated ex vivo using light transmission_x000D_
aggregation assay or by impedance aggregometry which measure platelet adhesion on a pair of electrode_x000D_
immersed in a whole blood sample. Although very simple and sensitive, theses two standardised in vivo_x000D_
procedures are very low throughput in nature, which makes them rapidly unpractical and expensive if one aims_x000D_
at establishing dose-toxicity curves early in the selection of promising lead candidates from compound_x000D_
libraries. To address this limitation, we will validate two cell-based assays using an electrical impedance_x000D_
technology in 96-well format to quantify drugs-induced endothelium permeability and platelet aggregation., program purpose french : As a world leader in the field of toxicology, Charles River Laboratories (CRL) is seeking to expand its_x000D_
portfolio of toxicology expertises through the development of novel cell-based assays. In this project, we_x000D_
propose to apply electric cell impedance sensing (ECIS) for the evaluation of functional end-point associated_x000D_
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 that_x000D_
vascular safety of drugs constitutes an important criterion in both the drug development and the drug approval_x000D_
processes. Drug-induced endothelium leakage is routinely tested in animal models by measuring Evans Blue_x000D_
endothelium extravasation in organs. Platelet function can be evaluated ex vivo using light transmission_x000D_
aggregation assay or by impedance aggregometry which measure platelet adhesion on a pair of electrode_x000D_
immersed in a whole blood sample. Although very simple and sensitive, theses two standardised in vivo_x000D_
procedures are very low throughput in nature, which makes them rapidly unpractical and expensive if one aims_x000D_
at establishing dose-toxicity curves early in the selection of promising lead candidates from compound_x000D_
libraries. To address this limitation, we will validate two cell-based assays using an electrical impedance_x000D_
technology in 96-well format to quantify drugs-induced endothelium permeability and platelet aggregation., agreement title english : Validation of cell impedance sensing as a high-throughput approach for toxicity evaluation in vitro, agreement title french : Validation of cell impedance sensing as a high-throughput approach for toxicity evaluation in vitro, agreement number : EGP, agreement value : 25000.0, agreement start date : 2018-02-07, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year (2017-2018 to 2018-2019)., additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier (2017-2018 à 2018-2019)., owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada