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Endothelial permeability

Since disruption of the endothelial layer is an important feature for many diseases, early screening of endothelial permeability is essential in the drug discovery process. Vascular leakage should be taken into account as well, being a dose-limiting adverse effect for many therapeutics under development. Our experts use a high-throughput, real-time and label-free technology to assess endothelial permeability, which allows in-depth analyses of vascular barrier function in health and disease for your drug discovery projects.

 

Benefits

Real-time monitoring
of barrier function disruption and recovery

Multiplexing assay
Noninvasive nature of the readout allows for multiple experiments

High quality results
Based on 10+ years of Ncardia experience

Description

Impedance assay

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.

Case Study

Capturing drug induced vascular leakage by chemotherapeutics

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

Assay Capabilities

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Related

Manufacturing Service  

Vascular endothelial cells

Poster  

Simultaneous measurement of contractility, electrophysiology and troponin I secretion to determine cardiotoxicity