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Stromal Cells Promote Neovascular Invasion Across Tissue Interfaces.

Hannah A Strobel1, Steven A LaBelle2,3, Laxminarayanan Krishnan4

  • 1Advanced Solutions Life Sciences, Manchester, NH, United States.

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|October 5, 2020
PubMed
Summary
This summary is machine-generated.

Growing blood vessels (neovessels) navigate tissue interfaces by being deflected by collagen matrix barriers. Stromal cells, using vascular endothelial growth factor-A (VEGF-A), guide this process for successful neovascularization.

Keywords:
VEGFneovessel invasionstromal cellstissue interfacevascular biology

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Area of Science:

  • Biomedical Engineering
  • Cell Biology
  • Tissue Engineering

Background:

  • Vascular connectivity is crucial for neovascularization and tissue regeneration.
  • Growing blood vessels (neovessels) must cross tissue interfaces during angiogenesis.
  • The mechanisms by which neovessels traverse tissue interfaces remain largely unknown.

Purpose of the Study:

  • To investigate how growing neovessels interact with and cross tissue interfaces.
  • To elucidate the role of the extracellular matrix and stromal cells in neovessel guidance at interfaces.
  • To understand the biomechanical and molecular factors governing neovascularization across tissue boundaries.

Main Methods:

  • Developed a 3D experimental model of angiogenesis with a collagen matrix interface.
  • Utilized computational modeling to analyze neovessel-matrix biomechanical interactions.
  • Investigated the role of stromal cells and vascular endothelial growth factor-A (VEGF-A) in interface crossing.

Main Results:

  • Matrix interfaces act as barriers, deflecting neovessels parallel to the interface.
  • Collagen fibril density and alignment at the interface guide neovessel trajectory.
  • Stromal cells, via a VEGF-A-dependent mechanism, facilitate neovessel crossing, but VEGF-A alone is insufficient.

Conclusions:

  • Tissue interfaces present biomechanical barriers to neovascularization.
  • Collagen matrix properties dictate neovessel deflection and guidance.
  • Stromal cells provide essential positional cues for neovascularization across interfaces, mediated by VEGF-A.