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Designing an accurate three‐dimensional blood‐brain barrier model ‐ fact or fiction?

The blood‐brain barrier (BBB) is an anatomical barrier formed by specialized brain endothelial cells surrounded by astrocytes and pericytes ‐ cells described to induce this BBB phenotype in endothelial cells. Specific cellular interactions are crucial for a proper BBB induction and their disruption during cerebral vascular diseases leads to barrier disruption. Most BBB in vitro models developed so far are limited by the 2‐dimensional nature of the model, use of only 2 of the three cell types that form the barrier as well as the absence of normal cellular interactions. In this study, we have developed a novel in vitro three‐dimensional BBB model. Brain endothelial cells form tube‐like structures in three‐dimensional matrices and astrocytes co‐cultured with the endothelial cells interact through astrocytic end‐feet contact as described in vivo. Recently we completed the model with pericytes. This model system will provide information on specific cellular interactions and signals that promote induction of BBB formation during development and can be readily subjected to different insults to understand BBB disruption.