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Human blood-brain barrier model: a physiologically relevant 2D human in vitro model

Endothelial cells of the blood-brain barrier (BBB) express unique combinations of enzymes and transport molecules. They are therefore unique and distinguishable from all other barrier-forming cells in the body.

To achieve therapeutic efficacy, a potential CNS drug has to cross the BBB. However, most small molecules and virtually all protein and peptide therapeutics do not cross the BBB.

Since we still lack a complete understanding of the in vivo BBB, a human in vitro BBB model can be used to obtain relevant human data when designed to predict human response. An in vitro BBB model is physiologically relevant not only when the cells express the BBB markers, but also when they are able to establish the right junctions, ensuring barrier integrity. Pluripotent stem cells offer the opportunity for BBB modeling. iPS-derived endothelial cells can be used to address neurodegenerative disease mechanistic questions and support drug screening campaigns.

The BBB model we have established at IRBM is based on endothelial cells derived from iPSCs. It is suitable for screening purposes due to high junctional tightness and expression of functional BBB markers.

The BBB model has been set up with different pharmacological classes of molecules that vary in size and, more importantly, use various mechanisms of brain entry. The model can be used as a permeability screen to investigate BBB permeation of new investigational compounds. This allows us to identify various physicochemical properties, including those compounds that are transporter substrates, whether or not the transporters involved have been identified.

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