VEGF-mediated fusion in the generation of uniluminal vascular spheroids.
Embryonic mouse allantoic tissue (E8.5) was cultured in hanging drops to generate a three-dimensional vascular micro-tissue. The resulting tissue spheroids had an inner network of small diameter vessels expressing platelet endothelial cell adhesion molecule-1 (PECAM-1) and an outer layer of cells expressing SMalphaA, SM22-alpha, and SM-MHC. In a subsequent phase of culture, the fusion-promoting activity of vascular endothelial growth factor (VEGF) was used to transform the inner network of small diameter endothelial tubes into a contiguous layer of cells expressing PECAM-1, CD34, and VE-cadherin that circumscribed a central lumen-like cavity. The blood vessel-like character of the VEGF-treated spheroids was further demonstrated by their physiologically relevant vasodilatory and contractile responses, including contraction induced by KCl and relaxation stimulated by high-density lipoproteins and acetylcholine-induced nitric oxide production.
Gentile
Carmine
C
Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Fleming
Paul A
PA
Mironov
Vladimir
V
Argraves
Kelley M
KM
Argraves
W Scott
WS
Drake
Christopher J
CJ
D000199:Actins / Q000378:metabolism; D000482:Allantois / Q000098:blood supply / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism; D006649:Histocompatibility Antigens / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D000199:Actins; D006649:Histocompatibility Antigens; D042461:Vascular Endothelial Growth Factor A