Pericytes and shear stress each alter the shape of a self-assembled vascular network

Blood vessel morphology is dictated by mechanical and biochemical cues. Flow-induced shear stress and pericytes both play important roles, and they have previously been studied using on-chip vascular networks to uncover their connection to angiogenic sprouting and network stabilization. However, it is unknown which shear stress values promote angiogenesis, how pericytes are directed to sprouts, and how shear stress and pericytes affect the overall vessel morphology. Here, we employed a microfluidic device to study these phenomena in three-dimensional (3D) self-assembled vasculature. Computational fluid dynamics solver (COMSOL) simulations indicated that sprouts form most frequently at locations of relatively low shear stresses (0.5-1.5 dyn cm(-2)). Experimental results show that pericytes limit vascular diameter. Interestingly, when treated with imatinib or crenolanib, which are chemotherapeutic drugs and inhibitors of platelet-derived growth factor receptor beta (PDGFR beta), the pericyte coverage of vessels decreased significantly but vessel diameter remained unchanged. This furthers our understanding of the mechanisms underlying vascular development and demonstrates the value of this microfluidic device in future studies on drug development and vascular biology.

Automated summary

Blood vessel morphology is influenced by mechanical and biochemical cues, such as flow-induced shear stress and pericytes. This study reveals that angiogenesis occurs at locations with relatively low shear stresses (0.5-1.5 dyn cm(-2)) and that pericytes regulate vascular diameter. Furthermore, inhibiting platelet-derived growth factor receptor beta decreases pericyte coverage without affecting vessel diameter.