47 Rue Adrienne Bolland
Our scientists assess endothelial permeability through impedance assays. This allows for monitoring of a wide range of physiological and pathophysiological mechanisms for drug discovery, to assess both compound safety and efficacy. Compared to other endothelial permeability assay types, like transwells, electrical impedance is more sensitive, and enables time-lapse tracking.
Our advanced data analysis capabilities enable calculation of time course changes in cell permeability, cell-matrix interaction and the cell membrane capacitance. Such analyses enable discrimination between necrosis and apoptosis and between subtle loss of cell-cell contacts or acute cell death.
Vascular leakage is a dose-limiting adverse effect for many therapeutics under development and should be taken into account. This study investigated the effect of 2 test compounds in a concentration range over 21 days with the endothelial permeability assay.
hiPSC-derived endothelial cells form a tight barrier that remains stable in long-term culture (graph A), which resembles the quiescent status of healthy endothelium in the human body. For this case study, the endothelial barrier function of hiPSC-derived endothelial cells was challenged with two model drugs for cancer treatment. Relevant and distinctive side effects on endothelial barrier functioning were defined: high concentrations of the DNA alkylating agent completely and irreversibly deteriorated barrier function (graph B), while the tubulin inhibitor treatment caused a transient opening of the barrier that could be restored after drug removal (graph C).
Click here to read the full case study: Capturing drug induced vascular leakage by chemotherapeutics
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