Mathematical modeling of the capillary-like pattern generated by adrenomedullin-treated human vascular endothelial cells in vitro

Dev Dyn. 2009 Aug;238(8):1951-63. doi: 10.1002/dvdy.22022.

Abstract

A recently proposed approach was used to model the self-organization into capillary-like structures of human vascular endothelial cells cultured on Matrigel. The model combines a Cellular Potts Model, considering cell adhesion, cytoskeletal rearrangement and chemotaxis, and a Partial Differential Equation model describing the release and the diffusion of a chemoattractant. The results were compared with the data from real in vitro experiments to establish the capability of the model to accurately reproduce both the spontaneous self-assembly of unstimulated cells and their self-organization in the presence of the pro-angiogenic factor adrenomedullin. The results showed that the model can accurately reproduce the self-assembly of unstimulated cells, but it failed in reproducing the adrenomedullin-induced self-organization of the cells. The extension of the model to include cell proliferation led to a good match between simulated and experimental patterns in both cases with predicted proliferation rates in agreement with the data of cell proliferation experiments.

MeSH terms

  • Adrenomedullin / pharmacology*
  • Base Sequence
  • Capillaries / cytology
  • Capillaries / drug effects*
  • Capillaries / growth & development*
  • Capillaries / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Collagen
  • DNA Primers / genetics
  • Drug Combinations
  • Endothelial Cells / cytology*
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Humans
  • In Vitro Techniques
  • Laminin
  • Models, Biological*
  • Neovascularization, Physiologic / drug effects*
  • Neovascularization, Physiologic / genetics
  • Phenotype
  • Proteoglycans
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Vascular Endothelial Growth Factor / genetics
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • DNA Primers
  • Drug Combinations
  • Laminin
  • Proteoglycans
  • RNA, Messenger
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • matrigel
  • Adrenomedullin
  • Collagen
  • Receptors, Vascular Endothelial Growth Factor