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In vitro Vasculogenesis Models Revisited - Measurementof VEGF Diffusion in Matrigel

Published online by Cambridge University Press:  11 July 2009

T. Miura  and
R. Tanaka
T. Miura*
Affiliation:
Department of Anatomy and Developmental Biology, Kyoto University Graduate School of Medicine JST CREST & PRESTO
R. Tanaka
Affiliation:
Department of Mathematics, Kyoto University Faculy of Science
*
miura_takashi@mac.com
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Abstract

The circulatory system is one of thefirst to function during development. The earliest event in thesystem's development is vasculogenesis, whereby vascularprogeniter cells form clusters called blood islands, which laterfuse to form capillary networks. There exists a very goodin vitro system that mimics this process. When HUVECs(Human Umbilical Vein Endothelial Cells) are cultured on Matrigel,they spontaneously form a capillary network structure. Twotheoretical models have been proposed to explain the patternformation of this in vitro system. Both models utilizechemotaxis to generate spatial instability, and one modelspecifies VEGF as the chemoattractant. However, there are severalunknown factors concerning the experimental model. First, thepattern formation process occurs at the interface between theliquid medium and Matrigel, and it is unclear whether diffusion inthe liquid or gel is critical. Second, the diffusion coefficientof VEGF, which determines the spatial scale of the capillarystructure, has not been properly measured. In the present study,we modified the experimental system to clarify the effect ofdiffusion in Matrigel, and experimentally measured the diffusioncoefficient of VEGF in this system. The relationship with thespatial scale of the pattern generated is discussed.

Keywords

pattern formationHUVECvascular endothelial growth factor (VEGF)diffusionMatrigel
Type
Research Article
Information
Mathematical Modelling of Natural Phenomena , Volume 4 , Issue 4: Morphogenesis , 2009 , pp. 118 - 130
Copyright
© EDP Sciences, 2009

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References

S. Gilbert. Developmental Biology. Sinauer, Massachusettes, 2003.
T. Sadler. Langman's Medical Embryology. Lippincott Williams & Wilkins, Maryland, 9th edition, 2004.
J. Murray. Mathematical biology. Springer - Verlag, Berlin, third edition, 2003.
W. Aird. Endothelial Biomedicine. Cambridge university press, 2007.
D. Manoussaki, S. Lubkin, R. Vernon, J. Murray. A mechanical model for the formation of vascular networks in vitro. Acta Biotheor, 44 (1996) No. 3-4, 271–282.
R. Merks, S. Brodsky, M. Goligorksy, S. Newman, J. Glazier. Cell elongation is key to in silico replication of in vitro vasculogenesis and subsequent remodeling. Dev Biol, 289 (2006) No. 1, 44–54.
G. Serini, D. Ambrosi, E. Giraudo, A. Gamba, L. Preziosi, F. Bussolino. Modeling the early stages of vascular network assembly. EMBO J, 22 (2003) No. 8, 1771–1779.
D. Berk, F. Yuan, M. Leunig, R. Jain. Fluorescence photobleaching with spatial fourier analysis: measurement of diffusion in light-scattering media. Biophys J, 65 (1993) No. 6, 2428–2436.
M. Chambard, J. Gabrion, J. Mauchamp. Influence of collagen gel on the orientation of epithelial cell polarity: follicle formation from isolated thyroid cells and from preformed monolayers. J Cell Biol, 91 (1981) No. 1, 157–166.
Miura, T.. Modulation of activator diffusion by extracellular matrix in turing system. RIMS Kokyuroku Bessatsu, B3 (2007), 165-176.
F. Crick. Diffusion in embryogenesis. Nature, 225 (1970) No. 5231, 420–422.
G. Reeves, C. Muratov, T. Schuepbach, S. Shvartsman. Quantitative models of developmental pattern formation. Dev Cell, 11 (2006) No. 3, 289–300.
Buelow, H., Hobert, O.. The molecular diversity of glycosaminoglycans shapes animal development. Annu Rev Cell Dev Biol, 22 (2006), 375–407. CrossRef
A. Okubo. Diffusion and ecological problems: mathematical models. Springer-Verlag, 1980.
Iida, M., Mimura, M., Ninomiya, H.. Diffusion, cross-diffusion and competitive interaction. J Math Biol, 53 (2006), 617-641. CrossRef
C. Nicholson, E. Sykova. Extracellular space structure revealed by diffusion analysis. Trends Neurosci, 21 (1998) No. 5, 207–215.
R. Thorne, C. Nicholson. In vivo diffusion analysis with quantum dots and dextrans predicts the width of brain extracellular space. Proc Natl Acad Sci U S A, 103 (2006) No. 14, 5567–5572.
F. Gelain, D. Bottai, A. Vescovi, S. Zhang. Designer self-assembling peptide nanofiber scaffolds for adult mouse neural stem cell 3-dimensional cultures. PLoS ONE, 1 (2006):e119.
P. Iglesias and P. Devreotes. Navigating through models of chemotaxis. Curr Opin Cell Biol, 20 (2008) No. 1, 35–40.
I. Barkefors, S. Le Jan, L. Jakobsson, E. Hejll, G. Carlson, H. Johansson, J. Jarvius, J. Park, N. Jeon, J. Kreuger. Endothelial cell migration in stable gradients of vascular endothelial growth factor a and fibroblast growth factor 2: effects on chemotaxis and chemokinesis. J Biol Chem, 283 (2008) No. 20, 13905–13912.
J. Park, G. Keller, N. Ferrara. The vascular endothelial growth factor (vegf) isoforms: differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound vegf. Mol Biol Cell, 4 (1993) No. 12, 1317–1326.
C. Ruhrberg, H. Gerhardt, M. Golding, R. Watson, S. Ioannidou, H. Fujisawa, C. Betsholtz, D. Shima. Spatially restricted patterning cues provided by heparin-binding vegf-a control blood vessel branching morphogenesis. Genes Dev, 16 (2002) No. 20, 2684–2698.