Three-dimensional biomimetic vascular model reveals a RhoA, Rac1, and <i>N</i> -cadherin balance in mural cell–endothelial cell-regulated barrier function

  • Stella Alimperti
    Department of Biomedical Engineering, Boston University, Boston, MA 02215;
  • Teodelinda Mirabella
    Department of Biomedical Engineering, Boston University, Boston, MA 02215;
  • Varnica Bajaj
    Department of Biomedical Engineering, Boston University, Boston, MA 02215;
  • William Polacheck
    Department of Biomedical Engineering, Boston University, Boston, MA 02215;
  • Dana M. Pirone
    Department of Science, Mount St. Mary’s University, Emmitsburg, MD 21727;
  • Jeremy Duffield
    Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA 98195;
  • Jeroen Eyckmans
    Department of Biomedical Engineering, Boston University, Boston, MA 02215;
  • Richard K. Assoian
    Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104;
  • Christopher S. Chen
    Department of Biomedical Engineering, Boston University, Boston, MA 02215;

説明

<jats:title>Significance</jats:title> <jats:p> Organ homeostasis requires integrity of blood vessels; alterations or disruption of the vascular barrier between blood and tissue contribute to numerous diseases. Endothelial cells and mural cells are two key cell types, which play significant roles for the maintenance of barrier function. Here, we present a 3D bicellular vascular model to mimic this barrier function and study the role of mural cells in vascular inflammation. Importantly, by using this 3D model we identified RhoA, Rac1, and <jats:italic>N</jats:italic> -cadherin as important regulators in mural–endothelial cell-mediated vascular barrier function. Given the recognized fundamental importance of this barrier in numerous disease settings, this in vitro microphysiological system presented herein could provide a tool for studying vascular barrier function in 3D microenvironments. </jats:p>

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