Abstract

Using Microchannels to Study Endothelium in vitro

Elisabeth Verpoorte, Professor, Pharmaceutical Analysis, University of Groningen

Microfluidic systems incorporating endothelial cell monolayers were among the earliest examples of organs-on-chips, with examples dating back almost two decades. This was to be expected, as microchannels are an obvious (though perhaps not perfect) mimic for the (micro)vascular system in terms of geometry. Moreover, microchannel-based in vitro systems also allow controlled application of shear stress, a crucial parameter in vivo that dictates endothelium properties. Despite this, microfluidic devices for determining shear-stress-dependent parameters like cellular morphology and endothelium permeability have been less common. In this presentation, I will present work done in our labs focusing on endothelial cell cultures in microfluidic channels and what these systems can teach us about vascular endothelium. We have worked primarily with human umbilical vein endothelial cell (HUVEC) culture in gelatin-coated glass or PDMS channels, and more recently with cells cultured on a gelatin substrate. HUVEC exhibit a clear morphological response to the surface material on which they are cultured, a response which can also be reflected in their gene expression. Moreover, cell alignment can be guided to some extent by culture in small channels and on defined gelatin features. More recently, we have considered microflow systems to study the permeability of endothelial cell monolayers in diabetes-associated microenvironments, by tracking the transport of fluorescently labelled albumin across these barriers into a gelatin layer underneath. Summarizing, in our experience even simple microchannel devices can provide insight into endothelium behaviour, under a variety of (patho)physiological conditions.