Past REU Participants & Project Pages

2006 REU Porjects
2006 REU Projects
2006 Participant: Keshia Ashe
Project Title: Modeling Endothelial Cell Proliferation in Response to Angiogenic Compounds

Faculty Advisor:Dr. Edward Botchwey
Introduction:
Angiogenesis is the method the by which the body creates new blood vessels in the face of damaged or destroyed vessels. However, the rate of this naturally-occurring phenomenon is not always conducive to timely healing. In response, researchers at the University of Virginia have been exploring techniques to control rates of angiogenesis by introducing drugs that stimulate endothelial cell proliferation and migration to form vessels. Drugs under investigation include SC-3-149, a small molecule inducer of angiogenesis, and Vascular Endothelial Growth Factor, a naturally-occurring compound. Drug encapsulation, delivery, and cell response are at the core of this study. While encapsulating drug in biodegradable polymer microspheres is favorable, the next step is determining the spatiotemporal diffusion profile of the drug and using this to predict responsive cell proliferation. Computational modeling is useful in this regard because can integrate parameters across several aspects of drug delivery and use empirically- and mathematically- derived equations to predict cell doubling. This project focused on developing doubling equations to govern cell proliferation in response to drug concentrations and how the two drugs previously mentioned are comparable given the same initial conditions.
Conclusion:
Given the correct doubling equation and diffusion parameters, agent-based computational modeling is a feasible method to predict cell doubling in response to drug concentrations. Although experimental and predicted doubling times for SC-3-149 were not equal, this could be due to differing drug treatment techniques (media-treated vs. diffusion from a microsphere). Over a 7 day time period, SC-3-149 is more effective in inducing endothelial cell proliferation than VEGF.
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