In vitro blood-brain barrier functional assays in a human IPSC-based model

Abstract

The blood-brain barrier (BBB) is a key biological interface that controls trafficking between the bloodstream and brain to maintain neural homeostasis. To carry out this role, the BBB exhibits several specialized properties, including limited permeability and active transporter function. These properties are often evaluated within in vitro BBB models, which can be utilized for high-throughput screening applications such as drug discovery. Here, we detail several common methods used to qualify in vitro BBB models, including measurement of transendothelial electrical resistance (TEER), determination of permeability coefficients (Pe) for small molecules, and assessment of efflux transporter activity. We describe these methods in the context of BBB endothelial cells derived from human-induced pluripotent stem cells (iPSCs), a model commonly employed in our research group.