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Interstitial fluid flow intensity modulates endothelial sprouting in restricted Src-activated cell clusters during

Rodrigo Hernández Vera1, Elsa Genové, Lery Alvarez

  • 1Center for Biomedical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

Tissue Engineering. Part A
|July 19, 2008
PubMed
Summary

Interstitial fluid flow significantly impacts capillary development in tissue engineering. Optimal flow velocities promote sprout length and branching by activating Src pathways in endothelial cells.

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Area of Science:

  • Biomedical Engineering
  • Cell Biology
  • Tissue Engineering

Background:

  • In vitro tissue development requires functional vascular networks for larger constructs.
  • Interstitial fluid flow and vascular endothelial growth factor are known to promote capillary morphogenesis and cell sprouting.

Purpose of the Study:

  • To investigate the effect of interstitial fluid flow velocities on capillary morphogenesis.
  • To understand the role of Src activation in flow-mediated vascular development.

Main Methods:

  • Utilized human umbilical vein endothelial cell monolayers.
  • Applied a range of interstitial flow velocities (0-50 microm/min).
  • Assessed capillary-like structure formation, sprout length, branching, and Src phosphorylation levels.

Main Results:

  • Interstitial flow did not significantly affect the number of capillary-like structures.
  • Sprout length and branching degree peaked at flow velocities of 10-20 microm/min.
  • Src phosphorylation levels also peaked at these optimal flow velocities, indicating localized activation.

Conclusions:

  • Interstitial fluid flow is a critical biophysical stimulus for capillary morphogenesis.
  • Optimal flow conditions enhance sprout elongation and branching through Src-dependent mechanisms.
  • Capillary morphogenesis is spatially regulated by flow-induced mechanical stimuli activating specific cell populations (pSrc).