Poor penetration of the Blood Brain Barrier is the cause for attrition for 95% of drugs developed for neurological disorders. As such, it is of great interest to explore potential molecules that can modulate BBB permeability
What Makes Our Blood Brain Barrier Assay Different?
Our BBB assay is unique in the sense that it is a triculture BBB model, composed of iPSC-derived human brain epithelial cells, human astrocytes, and human pericytes, seeded around a transwell. The transwell serves to establish both an apical (or “blood”) compartment and a basal (or “brain”) compartment, in which your test articles can be dosed and collected to determine permeability across the BBB. This co-culture set-up not only mimics the characteristics of the BBB in vivo but also increases the expression of tight junction proteins, occludin and claudin. The cells in our BBB model have been shown to express some of the key epithelial cell markers as well, such as BCRP, GLUT-1, MRP1, transferrin, P-gp, ZO-1, CD98hc, VE-cadherin, and CD31.
Figure 1. Brain Microvascular Endothelial Cells (Blue) are cultured on the top of the transwell and Pericytes and Astrocytes are cultured (Orange and Green) on the bottom of the transwell to form a barrier that mimics an in vivo model.
General Procedure
- 3D Blood Brain Barrier models are cultured over 4 days to establish a viable barrier as measured by transendothelial electrical resistance (> 150 Ω x cm2). On the fifth day, the models are dosed with test articles for twenty-four hours.
- If assessment of alterations to BBB permeability due to drug treatment is required, a four-compound control panel is added to wells.
- Media is sampled for quantitation of test articles by LCMS/MS.
- Apparent permeability is calculated.
If you are interested in working with us and utilizing this novel BBB assay, please reach out to our team today to discuss further. We offer end-to-end solutions leveraging this assay from compound to report.