Interstitial flow regulates in vitro three-dimensional self-organized brain micro-vessels

Cell culture under medium flow has been shown to favor human brain microvascular endothelial cells function and maturation. Here a three-dimensional in vitro model of the human brain microvasculature, comprising brain microvascular endothelial cells but also astrocytes, pericytes and a collagen type I microfiber – fibrin based matrix, was cultured under continuous medium flow in a pressure driven microphysiological system (10 kPa, in 60–30 s cycles). The cells self-organized in micro-vessels perpendicular to the shear flow. Comparison with static culture showed that the resulting interstitial flow enhanced a more defined micro-vasculature network, with slightly more numerous lumens, and a higher expression of transporters, carriers and tight junction genes and proteins, essential to the blood-brain barrier functions. [Display omitted] •Culture under continuous interstitial flow of a 3D in vitro brain micro-vessel model.•A more defined brain microvasculature after 7 days under flow culture.•No significant change in lumen diameters, but a tendency for more numerous lumen.•Flow stress enhanced gene expression of tight junction, transporters and carriers.•Same tendency for protein expression.