Improved microvascular network in vitro by human blood outgrowth endothelial cells relative to vessel-derived...

Evidence suggests that bone marrow-derived cells circulating in adult blood, sometimes called endothelial progenitor cells, contribute to neovascularization in vivo and give rise to cells expressing endothelial markers in culture. To explore the utility of blood-derived cells expressing an endothelial phenotype for creating tissue-engineered microvascular networks, we employed a three-dimensional in vitro angiogenesis model to compare microvascular network formation by human blood outgrowth endothelial cells (HBOECs) with three human vessel-derived endothelial cell (EC) types: human umbilical vein ECs (HUVECs), and adult and neonatal human microvascular ECs. Under every condition investigated, HBOECs within collagen gels elongated significantly more than any other cell type. Under all conditions investigated, gel contraction and cell elongation were correlated, with HBOECs demonstrating the largest generation of force. HBOECs did not exhibit a survival advantage, nor did they enhance elongation of HUVECs when the two cell types were cocultured. Network formation of both HBOECs and HUVECs was inhibited by blocking antibodies to alpha2beta1, but not alpha(v)beta3, integrins. Taken together, these data suggest that superior network exhibited by HBOECs relative to vessel-derived endothelial cells is not due to a survival advantage, use of different integrins, or secretion of an autocrine/paracrine factor, but may be related to increased force generation.