Pericytes Repair Engineered Defects in the Basement Membrane to Restore Barrier Integrity in an in vitro Model of the Blood-Brain Barrier.

Pericytes play a key role in the brain where they support the blood-brain barrier (BBB). Their loss has been reported in response to systemic inflammation and neurodegenerative disease. We recently demonstrated that iPSC-derived brain pericyte-like cells (BPLCs) and brain microvascular endothelial cell (BMEC)-like cells collaboratively form a nascent, 3D basement membrane when cultured across a nanoporous membrane1. Building on this, we aimed to engineer defects in the basement membrane to investigate whether pericytes could facilitate its repair. In BMEC monocultures, we observed that micropore patterns in nanomembranes created discontinuities in laminin, which destabilized barrier function. Remarkably, the addition of pericytes to the basal side of the membrane restored both laminin integrity and barrier function. Our results align with the role of pericytes as support cells for microvasculature and encourage the use of our tissue barrier platform (the {micro}SiM) to model neurological disorders involving pericyte dysfunction and/or disruption of basement membrane.