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Flow‐mediated Vessel Guidance
Author(s) -
Song Jonathan W.,
Bazou Despina,
Munn Lance L.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.688.3
Subject(s) - lymphangiogenesis , angiogenesis , microbiology and biotechnology , sprouting angiogenesis , organ on a chip , endothelium , blood vessel , vascular endothelial growth factor , interstitial space , interstitial fluid , lymphatic system , shear stress , chemistry , biology , neovascularization , anatomy , pathology , immunology , medicine , nanotechnology , materials science , cancer research , microfluidics , vegf receptors , endocrinology , cancer , genetics , composite material , metastasis
Endothelial cells (ECs) comprising the inner lining of blood vessels are continually exposed to mechanical forces due to fluid flow, but our knowledge of the determinants of EC sprouting and vessel guidance has focused primarily on factors that signal biochemically. Progress in understanding how ECs sense fluid forces during sprouting has been impaired by the lack of systems that can monitor angiogenesis while controlling both the fluidic and biochemical microenvironments. We developed 3‐D angiogenesis‐on‐a chip (AoC) technology that allows for simultaneous application of intraluminal fluid shear stress, transendothelial interstitial flow, and vascular endothelial growth factor (VEGF) gradient conditions to pre‐formed vessel analogues in vitro . We discovered that like VEGF gradients, the orientation of interstitial flow relative to the endothelium is crucial for triggering polarized vessel sprouting in a RhoA dependent manner. Moreover, we extend the principles of flow‐mediated vessel guidance to lymphangiogenesis to provide insights into the synergies between interstitial flow and the assembly of functional lymphatic vessels in vitro .