Modeling angiogenesis in the human brain in a tissue-engineered post-capillary venule

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.