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Publication Detail
Mechanobiology of Vascular Morphogenesis
  • Publication Type:
    Poster
  • Authors:
    Shahrezagamasaei S, Moeendarbary E, Javanmardi Y, Kamm R, Ari Whisler J
  • Presented date:
    05/06/2019
  • Presented at:
    CellMech 2019
  • Location:
    Milan, Italy
  • Addresses:
    Somayeh Shahreza
    University College London
    Mechanical Engineering
    Torrington Place
    London
    WC1E 7JE
    United Kingdom
Abstract
Vascular in-vitro models not only will enable us to understand the vasculogenesis and angiogenesis mechanisms but also will provide us with a great and reliable platform to study cancer metastasis, angiotherapy, anti-angiotherapy, test drugs, and vascularize engineered tissue/organs which is the most significant inability to engineer and develop such constructs. Owing to differentiation, migration, proliferation, elongation and inherent ability of endothelial cells (ECs) to self-assemble, vasculogenesis and angiogenesis occur in the human body during embryogenesis and adulthood. However, several other cell types, among them fibroblasts (FBs), the most common cells of connective tissue, play important roles in the regulation of vasculogenesis and angiogenesis. Although the roles of chemical interactions between ECs and FBs on vascular processes have been investigated extensively, still we lack ground understanding of how mechanical interactions support the formation of vascular networks. However, to create a physiologically more relevant in vitro vascular models which resemble in vivo, it is crucial to consider the role of mechanical cues along with chemical determinants. Applying a three-channel microfluidic device, we encapsulated ECs with FBs in a 3D fibrin matrix and treated them with several mechanotransduction chemical inhibitors against three genes, Rho, SRC, and YAP, belonging to mechanotransduction pathways to perturb cellular contractility and force generation and investigate the role of mechanical forces in vessel formation. Imaging techniques and dextran perfusion showed that compared to the controls either no networks formed in the inhibitor-treated devices or there were not functional networks which indicate the importance of mechanical forces in vessel formation.
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