Interstitial flow regulates the angiogenic response and phenotype of endothelial cells in a 3D culture model

A crucial yet ill-defined phenomenon involved in the remodeling of vascular networks, including angiogenic sprouting, is flow-mediated endothelial dynamics and phenotype changes. Despite interstitial flow (IF) being ubiquitously present in living tissues surrounding blood capillaries, it is rarely investigated and poorly understood how endothelial cells respond to this flow during morphogenesis. Here we develop a microfluidic 3D in vitro model to investigate the role of IF during vasculogenic formation and angiogenic remodeling of microvascular networks. In the presented model, human blood endothelial cells co-cultured with stromal fibroblasts spontaneously organize into an interconnected microvascular network and then further expand to adjacent avascular regions in a manner of neovessel sprouting. We found that in the presence of IF, vasculogenic organization of the microvascular networ…