Analysis of Inward Vascular Remodeling Focusing on Endothelial–Perivascular Crosstalk in a Microfluidic Device

Abstract

Vascular remodeling is a crucial process for the effective delivery of oxygen and nutrients to the entire body during vascular formation. However, detailed mechanisms underlying vascular remodeling are not yet fully understood owing to the absence of an appropriate experimental model. To address this, in this study, we utilized a microfluidic vascular model with perivascular cells to investigate the mechanism of vascular remodeling by culturing human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (MSCs) in a microfluidic device. We compared two different cell culture conditions: culturing HUVECs and MSCs (1) separately in different channels and (2) in the same channel. In both conditions, microvascular networks covered with perivascular cells were formed. Interestingly, a significant inward vascular remodeling occurred over time when HUVECs and MSCs were cultured in different channels. This remodeling was mediated by direct endothelial–perivascular crosstalk through α6 integrin. Furthermore, computational fluid analysis revealed that hypothetical shear stress on the luminal surface of microvessels was attenuated during inward vascular remodeling, suggesting that the remodeling might be an adaptive change. Our findings and the microfluidic model will be useful not only for further elucidation of mechanisms underlying physiological and pathological vascular remodeling but also for constructing functional vascularized tissues and organs by controlling vascular remodeling.