Authors

Discussion

The blood-brain barrier (BBB) is a specialized network of cells that function to maintain a tightly controlled microenvironment around the brain. For many years, the scientific community has needed a robust and human-relevant BBB model to evaluate barrier function and its role in drug permeability in vitro, as well as to study diseases that affect it. The power of iPSC technology provides access to specialized cell types of the brain required to assemble such a model system, but the field has been challenged with generating cells that contain the appropriate markers, manufacturing a consistent supply of cells at-scale, and cryopreserving material for subsequent on-demand use. As a leader in iPSC technology and innovation, FUJIFILM Cellular Dynamics has generated and characterized 3 unique human iPSC-derived cell types for use in BBB model development, including astrocytes, brain microvascular endothelial cells (BMEC), and pericytes. Perhaps most notably, the differentiation and cryopreservation of BMEC to yield a cell type with distinctive morphological (cobblestone and tightly packed), structural (proper organization of tight junctions and appropriate expression of transporters), and functional (effective barrier formation) features that differ from other vascular endothelial cells lining peripheral blood cells has made the highest impact. Additionally, optimized media and supplements to enable long-term survival of 3 cell types in co-culture and to promote superior functional performance in transendothelial electrical resistance (TEER) assays is a key factor in the establishment of a reliable BBB model. The potential to integrate this system with emerging organ-on-a-chip technologies and other 3D cell culture systems offers an exciting new capability for the drug discovery community to advance the understanding of BBB function with respect to human health and disease.