Organized type I collagen influences endothelial patterns during “spontaneous angiogenesis in vitro”: Planar cultures as models of vascular development

Robert B. Vernon*, Stephanie L. Lara, Christopher J. Drake, M. Luisa Iruela-Arispe, John C. Angello, Charles D. Little, Thomas N. Wight, E. Helene Sage

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

108 Scopus citations


Selected strains of vascular endothelial cells, grown as confluent monolayers on tissue culture plastic, generate flat networks of cellular cords that resemble beds of capillaries—a phenomenon referred to as “spontaneous angiogenesis in vitro”. We have studied spontaneous angiogenic activity by a clonal population (clone A) of bovine aortic endothelial cells to indentify processes that mediate the development of cellular networks. Confluent cultures of clone A endothelial cells synthesized type I collagen, a portion of which was incorporated into narrow, extracellular cables that formed a planar network beneath the cellular monolayer. The collagenous cables acted as a template for the development of cellular networks: flattened, polygonal cells of the monolayer that were in direct contact with the cables acquired spindle shapes, associated to form cellular cords, and became elevated above the monolayer. Networks of cables and cellular cords did not form in a strain of bovine aortic endothelial cells that did not synthesize type I collagen, or when traction forces generated by clone A endothelial cells were inhibited with cytochalasin D. In a model of cable development, tension applied by a confluent monolayer of endothelial cells reorganized a sheetlike substrate of malleable type I collagen into a network of cables via the formation and radial enlargement of perforations through the collagen sheet. Our results point to a general involvement of extracellular matrix templates in two-dimensional (planar) models of vascular development in vitro. For several reasons, planar models simulate invasive angiogenesis poorly. In contrast, planar models might offer insights into the growth and development of planar vascular systems in vivo.

Original languageEnglish (US)
Pages (from-to)120-131
Number of pages12
JournalIn Vitro Cellular & Developmental Biology - Animal: Journal of the Society for In Vitro Biology
Issue number2
StatePublished - Feb 1995


  • angiogenesis
  • collagen
  • endothelial cell
  • extracellular matrix
  • in vitro
  • vasculogenesis

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology


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