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Updated: Aug 14, 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
Embryonic stem cells: a novel tool for the study of antiangiogenesis and tumor-induced angiogenesis
M Wartenberg1, F Dönmez, P Budde
1Department of Cell Biology, GKSS Research Center Teltow, Teltow, Germany.
Abstract:
Major research initiatives in antiangiogenesis research have been undertaken to control angiogenic diseases such as polyarthritis, psoriasis, endometriosis, and diabetic retinopathy, and inhibition of tumor-induced angiogenesis has emerged as one of the most promising anti-cancer therapies currently available. Although several quantitative in vivo (i.e., animal models) as well as in vitro (i.e., pure endothelial cell cultures) angiogenesis assays have been described, the development of novel angiogenesis assays with organotypic culture systems that take into account oxygen and nutrient gradients, depth-dependent changes in intracellular pH and a redox state similar to that found in a natural tissue microenvironment are necessary to investigate blood vessel growth. Embryonic stem cells of mouse and human origin have the capacity to develop into three-dimensional tissues with functional capillaries, and this model system represents an excellent in vitro model for antiangiogenesis research. Upon confrontation of stem cells by co-culture with multicellular tumor spheroids, tumor-induced angiogenesis, i.e., the invasion of endothelial host-derived cells into a tumor tissue, can also be monitored. The current review provides an overview of embryonic stem cells as novel tools for antiangiogenesis research and outlines the use of confrontation cultures for the study of tumor-induced angiogenesis.
Insights
Embryonic stem cells offer a novel in vitro model for antiangiogenesis research. This approach allows for studying tumor-induced angiogenesis by co-culturing stem cells with tumor spheroids.
Area of Science:
- Biomedical research
- Cell biology
- Cancer therapy
Background:
- Antiangiogenesis research targets diseases like cancer, polyarthritis, and diabetic retinopathy.
- Current in vitro and in vivo angiogenesis assays lack the complexity of a natural tissue microenvironment.
- Novel assays are needed to replicate oxygen/nutrient gradients and intracellular conditions found in vivo.
Purpose of the Study:
- To review embryonic stem cells as a novel tool for antiangiogenesis research.
- To outline the use of confrontation cultures for studying tumor-induced angiogenesis.
- To highlight the need for advanced in vitro models mimicking natural tissue conditions.
Main Methods:
- Utilizing mouse and human embryonic stem cells to form three-dimensional tissues with functional capillaries.
- Employing confrontation cultures of stem cells with multicellular tumor spheroids.
- Monitoring the invasion of host-derived endothelial cells into tumor tissue.
Main Results:
- Embryonic stem cell-derived tissues provide a functional in vitro model for antiangiogenesis studies.
- Confrontation cultures enable monitoring of tumor-induced angiogenesis, specifically endothelial cell invasion.
- This model system effectively simulates key aspects of the natural tissue microenvironment.
Conclusions:
- Embryonic stem cells represent a promising in vitro model for antiangiogenesis research.
- Confrontation cultures with stem cells are valuable for studying tumor-induced angiogenesis.
- This approach advances the development of anti-cancer therapies by better understanding angiogenesis.
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