Biomimetic model to reconstitute angiogenic sprouting morphogenesis in vitro

Area of Science:

• Biomedical Engineering
• Cell Biology
• Vascular Biology

Background:

• Angiogenesis, the formation of new blood vessels, is crucial for development and disease.
• Existing in vitro models often fail to fully recapitulate the complex 3D microenvironment and multicellular dynamics of in vivo angiogenesis.

Purpose of the Study:

• To engineer a novel 3D organotypic model for studying angiogenic sprouting and neovessel formation.
• To utilize this model to screen angiogenic factors and inhibitors, elucidating molecular mechanisms of neovascularization.

Main Methods:

• Engineered a 3D extracellular matrix model with preformed artificial vessels.
• Screened angiogenic factors and inhibitors, observing endothelial cell sprouting and structural development.
• Analyzed tip cell filopodia formation and vessel sprouting in response to molecular modulators.

Main Results:

• Identified two factor cocktails promoting robust multicellular endothelial sprouting.
• Observed hallmark features of in vivo angiogenesis, including tip/stalk cell dynamics and lumen formation.
• Demonstrated context-dependent effects of VEGF receptor 2 inhibition and distinct roles for sphingosine-1-phosphate and MMPs in sprouting.

Conclusions:

• The developed 3D biomimetic model accurately reconstitutes the morphogenetic steps of angiogenic sprouting.
• The model provides a powerful platform for investigating the molecular regulation of neovascularization.
• Findings suggest context-dependent VEGF signaling and highlight the utility of this model for drug discovery and mechanistic studies.