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Updated: May 22, 2026
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In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing
Published on: May 11, 2021
RAIN-Droplet: a novel 3D in vitro angiogenesis model
Benjamin D Zeitlin1, Zhihong Dong, Jacques E Nör
1Angiogenesis Research Laboratory, Department of Restorative Sciences, University of Michigan School of Dentistry, Ann Arbor, USA. bzeitlin@pacific.edu
Summary
A new Responsive Angiogenic Implanted Network (RAIN)-Droplet model enables 3D angiogenesis studies. This model revealed a surprising pro-angiogenic effect of sorafenib at low doses, impacting cancer drug development.
Area of Science:
- * Biomedical Engineering
- * Cancer Biology
- * Pharmacology
Background:
- * Angiogenesis is crucial for cancer growth and metastasis.
- * Existing in vitro angiogenesis models are limited.
- * Novel experimental tools are needed for drug screening.
Purpose of the Study:
- * Introduce the Responsive Angiogenic Implanted Network (RAIN)-Droplet model.
- * Develop a novel 3D angiogenesis assay.
- * Investigate drug effects on angiogenesis.
Main Methods:
- * Encapsulation of microvascular endothelial cells in self-assembling hydrogel droplets.
- * Embedding droplets in 3D matrices to observe sprout formation.
- * Testing bevacizumab and sorafenib for anti-angiogenic and pro-angiogenic effects.
Main Results:
- * RAIN-Droplet model successfully formed pre-formed angiogenic networks and capillary-like sprouts.
- * Bevacizumab significantly inhibited sprout formation.
- * Low-dose sorafenib demonstrated a novel pro-angiogenic effect, while high doses were inhibitory.
Conclusions:
- * The RAIN-Droplet model is a versatile 3D tool for studying vascular morphogenesis and drug testing.
- * Sorafenib exhibits a dose-dependent dual role in angiogenesis.
- * Findings may influence clinical applications and dosing of sorafenib in cancer therapy.
