Brain pericytes: from origins to implications in cell–cell communication within the neurovascular unit

The BBB is a natural barrier located in the endothelial cells of the cerebral microvessels (BMECs) that restricts exchanges between the bloodstream and the cerebral parenchyma. The integrity of the BBB is vital for preserving cerebral homeostasis, and neuroinflammatory processes alter the physical and/or metabolic properties of this barrier. The brain pericyte, which shares a common basement membrane with BMECs, has been shown to be a major cell type involved in the induction and maintenance of the BBB's main features. This presentation will review the role and intercellular interactions of human brain pericytes (hBPs) with the cells of the neurovascular unit, and particularly BMECs, based on data generated within the lab using proteomics, cell physiology, and studies of extracellular vesicles (EVs). The protein pattern of hBPs is modified once they are cocultured with BMECs, highlighting a metabolic switch induced by BMECs on hBPs. A stimulation of EV biogenesis is observed, indicating a potential need for a hBP-derived cell–cell communication through EVs. The mechanisms of interaction between BMECs and hBP-derived EVs are in favor a clathrin-coated pit-mediated endocytosis. Under inflammation, hBP-derived EVs exhibit a modified protein pattern compared to untreated EVs and induce a dysregulation of trans-endothelial electric resistance (TEER) on BMECs.

Despite their former reputation as a contaminant for BBB modeling in vitro, hBPs remain of importance for maintaining the BBB phenotype. BMECs also modulate the functions and developmental fates of hBPs. This work opens perspectives on the role of hBP-derived EVs on BBB feature regulation.