VEGF-mediated fusion in the generation of uniluminal vascular spheroids

Authors

  • Carmine Gentile,

    1. Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina
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    • C. Gentile and P.A. Fleming contributed equally to this work.

  • Paul A. Fleming,

    1. Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina
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    • C. Gentile and P.A. Fleming contributed equally to this work.

  • Vladimir Mironov,

    1. Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina
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  • Kelley M. Argraves,

    1. Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina
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  • W. Scott Argraves,

    1. Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina
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  • Christopher J. Drake

    Corresponding author
    1. Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina
    • Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, SC 29425
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Abstract

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 SMαA, SM22-α, 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. Developmental Dynamics 237:2918–2925, 2008. © 2008 Wiley-Liss, Inc.

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