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Tumor Endothelial Co-culture for On-chip Drug Testing Reem Ali, Simrit Safarulla, Vikram Surendran, Arvind Chandrasekaran CBBE, COE, NCA&T Tumor angiogenesis plays a crucial role in cancer progression. The tumor vasculature interface exhibits aggressive disruption of the endothelial lining of blood vessels, mediated by the release of pro-angiogenic factors, by the tumor. Endothelial disruption allows the blood vessels to become permeable, enabling angiogenesis towards the tumor and ultimately, circulation of tumor cells into the bloodstream. Angiogenic sprouting is characterized by disruption of the endothelial adherens junction, adoption of tip-cell phenotype, and sprouting. Our previous work has successfully shown endothelial disruption by tumor stimulation through an On-Chip culture. Given the nature of that particular culture, angiogenic sprouting is difficult to image due to the orientation of cells. We have developed a new segregated co- culture platform that enables the examination of individual cell populations through an on- demand ECM introduction. When segregating the cell types, and not giving them a medium to migrate within, we impede chemotaxis while still allowing for interaction. This allows for the facilitation of cell dynamics and enables observation of cell responses based solely on signaling. Endothelial disruption occurs without the ECM, but the effect on sprouting is unknown. We seek to understand the mechanism behind angiogenic dynamics and explore the role of the ECM in angiogenic sprouting.

Publication Date

4-1-2025

Keywords

Angiogenesis, Tumor-Vasculature Interface, Vascular Endothelial Growth Factor

Biomimetics of Pro-angiogenic Endothelial Dysregulations Enabled by Segregated Tumor Endothelial Co-culture for On-chip Drug Testing

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