iPSC-Derived Brain Endothelium Exhibits Stable, Long-Term Barrier Function in Perfused Hydrogel Scaffolds

We describe the construction a 3D blood-brain barrier model comprised of iPSC-derived brain endothelium cultured in channels within gelatin hydrogels. The iPSC-derived brain endothelium displays key features of the blood-brain barrier phenotype, including tight junction formation, efflux transporter activity, low paracellular permeability, and suppressed levels of transcytosis compared to non-blood-brain barrier endothelial controls. Collectively, this work provides the foundation for a fully human, biomimetic neurovascular model to study BBB in health and disease. iPSC-derived brain endothelium was cultured in 3D channels in gelatin hydrogels and analyzed for key signatures of blood-brain barrier phenotype. RNA-seq was used to assess changes in global gene expression signatures between endothelium cultured for one day under static conditions and fourteen days under perfused conditions.