Endogenous tissue contractility spatially regulates the VEGF signaling and angiogenesis in self-organizing microfabricated tissues

N. Rivron, E. Vrij, J. Rouwkema, R. Truckenmüller, S. le Gac, A. van den Berg, C. van Blitterswijk

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    Abstract

    Endogenous physical forces can drive the organization of tissues (1-2). The underlying mechanisms are currently based on cell surface mechanics (3) or mechanotransduction (4) and are thus separated from known conserved mechanisms including the formation of morphogen gradients. Here using an array of autonomously contracting and deforming, 3D, microfabricated, tissues, we show that tissue geometry and endogenous contractility spatially regulates the Vascular Endothelial Growth Factor (VEGF) signaling and the local formation of vascular patterns. The microfabricated tissues stereotypically and heterogeneously changed shape, compacted and formed robust patterns of vascular structures in regions of high deformation. This emergence correlated with the local over-expression of the receptor VEGFR2 and with the formation of a tissue-scale gradient of VEGF. We propose that endogenous tissue contractility and deformation is a morphogenetic regulator of angiogenesis, a finding which should stimulate new therapeutic strategies for vascular diseases and regenerative medicine.
    Original languageEnglish
    Pages (from-to)97-97
    JournalHistology and histopathology
    Volume26
    Issue numberSuppl. 1
    Publication statusPublished - 7 Jun 2011
    EventTERMIS-EU Chapter Meeting 2011 - Granada Congress and Exhibition Centre, Granada, Spain
    Duration: 7 Jun 201110 Jun 2011

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