Directing the flow of medium in controlled cocultures of HeLa cells and human umbilical vein endothelial cells with a microfluidic device.

A microfluidic device was integrated with a controlled coculture system of HeLa cells and human umbilical vein endothelial cells (HUVECs). This integrated assembly allowed control of the direction of flow of medium (along with signaling factors secreted from cells) across the cultured cells. We grew HeLa cells and HUVECs to confluency on separate substrates and then joined the two substrates. A microfluidic device was then assembled onto the substrates and a cell coculture was initiated with controlled perfusion of the medium. When the medium flow was directed from the HeLa side to the HUVEC side, the HUVECs retreated and the HeLa cells migrated into the newly vacated areas. By contrast, when the medium flow was in the opposite direction, there was essentially no net movement of either cell type. Our results suggest that the migration of HeLa cells and HUVECs in coculture was likely mediated by soluble factors produced by HeLa cells.