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Updated: Apr 21, 2026
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
A quantitative microfluidic angiogenesis screen for studying anti-angiogenic therapeutic drugs
Choong Kim1, Junichi Kasuya, Jessie Jeon
1Departments of Biological Engineering and Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. rdkamm@mit.edu.
Abstract:
Anti-angiogenic therapy, which suppresses tumor growth by disrupting oxygen and nutrient supply from blood to the tumor, is now widely accepted as a treatment for cancer. To investigate the mechanisms of action of these anti-angiogenesis drugs, new three dimensional (3D) cell culture-based drug screening models are increasingly employed. However, there is no in vitro high-throughput screening (HTS) angiogenesis assay that can provide uniform culture conditions for the quantitative assessment of physiological responses to chemoattractant reagents under various concentrations of anti-angiogenesis drugs. Here we describe a method for screening and quantifying the vascular endothelial growth factor (VEGF)-induced chemotactic response on human umbilical vein endothelial cells (HUVECs) cultured with different concentrations of bortezomib, a selective 26S proteasome inhibitor. With this quantitative microfluidic angiogenesis screen (QMAS), we demonstrate that bortezomib-induced endothelial cell death is preceded by a series of morphological changes that develop over several days. We also explore the mechanisms by which bortezomib can inhibit angiogenesis.
Insights
This study introduces a new microfluidic assay to screen anti-angiogenesis drugs. The quantitative microfluidic angiogenesis screen (QMAS) assesses bortezomib
Area of Science:
- Oncology
- Cell Biology
- Biotechnology
Background:
- Anti-angiogenic therapy is crucial for cancer treatment, targeting tumor blood supply.
- Three-dimensional (3D) cell culture models are vital for investigating anti-angiogenesis drug mechanisms.
- Existing in vitro assays lack uniform conditions for quantitative assessment of drug effects on angiogenesis.
Purpose of the Study:
- To develop and validate a high-throughput screening assay for quantifying angiogenesis.
- To investigate the effects of bortezomib on vascular endothelial growth factor (VEGF)-induced chemotaxis in human umbilical vein endothelial cells (HUVECs).
- To explore the mechanisms by which bortezomib inhibits angiogenesis.
Main Methods:
- Development of a quantitative microfluidic angiogenesis screen (QMAS).
- Culturing HUVECs under varying concentrations of bortezomib.
- Assessing VEGF-induced chemotactic response and morphological changes using QMAS.
Main Results:
- QMAS enables quantitative assessment of angiogenesis under drug treatment.
- Bortezomib induces endothelial cell death preceded by distinct morphological changes over several days.
- The study elucidates mechanisms of bortezomib-induced inhibition of angiogenesis.
Conclusions:
- QMAS is a robust platform for evaluating anti-angiogenesis drugs.
- Bortezomib's anti-angiogenic effects involve morphological changes and cell death.
- This assay advances the understanding of anti-angiogenesis drug action and screening.
