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Mechanism of Angiogenesis01:10

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Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
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The Arteriovenous AV Loop in a Small Animal Model to Study Angiogenesis and Vascularized Tissue Engineering
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Modeling angiogenesis in the human brain in a tissue-engineered post-capillary venule.

Nan Zhao1, Sarah Kulkarni2, Sophia Zhang3

  • 1Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, 21218, USA.

Angiogenesis
|February 16, 2023
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Summary

This study reveals that both brain endothelial cells and pericytes can lead angiogenesis. Pericyte-led sprouts grow twice as fast, highlighting their crucial role in brain vascularization.

Keywords:
AngiogenesisAngiogenic sproutBlood-brain barrierPericytesTip cellTissue engineering

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cell Biology

Background:

  • Angiogenesis is vital for development, repair, and disease, but poorly understood in the mature brain.
  • Existing models lack the resolution to study brain angiogenesis dynamics in detail.

Purpose of the Study:

  • To investigate angiogenesis in a tissue-engineered model of the mature brain vasculature.
  • To compare sprout dynamics led by brain endothelial cells versus pericytes.
  • To assess the impact of growth factor gradients on angiogenic sprouting.

Main Methods:

  • Utilized a tissue-engineered post-capillary venule (PCV) model.
  • Incorporated stem cell-derived induced brain microvascular endothelial-like cells (iBMECs) and pericyte-like cells (iPCs).
  • Visualized and quantified angiogenesis under perfusion and concentration gradient conditions.

Main Results:

  • Both iBMECs and iPCs can act as tip cells initiating angiogenic sprouts.
  • Pericyte-led sprouts exhibited a growth rate approximately twofold higher than endothelial cell-led sprouts.
  • Angiogenic sprouts showed a slight directional bias towards higher growth factor concentrations.
  • Pericytes displayed diverse behaviors, including quiescence, co-migration, or leading sprout formation.

Conclusions:

  • Pericytes are key regulators of angiogenesis in the brain, capable of leading sprout formation with enhanced growth rates.
  • The engineered PCV model provides a novel platform for studying brain angiogenesis dynamics.
  • Understanding pericyte roles is critical for addressing diseases involving brain vascularization.