Pericytes promote more angiogenesis and vasculogenesis than mesenchymal stromal cells in microfluidic chips

Abstract

The pericyte is a key player in vascularization, protecting endothelial cells from external harm and promoting formation of new vessels and connections when necessary. However, pericytic identity and its relation with other cell types, such as the mesenchymal stromal/stem cells, is highly debated. To compare the behaviour of pericytes and unselected stromal cells in vascularization, we used multichannel microfluidic chips to replicate the two processes of vessel formation: vasculogenesis, the de novo vessel formation, and angiogenesis, the sprouting of new vessels from existing ones. In angiogenesis, pericytes promote significantly more and longer sproutings than stromal cells. In vasculogenesis, stromal cells promote the formation of structures ressembling the embryonic capillary plexus, whereas pericytes wrap around the endothelial cells, arresting their division and forcing them into tubulogenesis. Whole-transcriptome sequencing confirms an upregulation of pro-vascularization and cytostatic genes in co-cultures of pericytes and endothelial cells; while stromal cells strongly stimulate mitosis and organelle biogenesis pathways and decrease the release of pro-inflammatory cytokines. In this study, we offer new insights into the pericyte-endothelial cell relation and the mesenchymal stromal cell elusive identity, relevant in both vascular biology and tissue engineering.