Katy Lassahn

MS Thesis Defense
June 3rd, 2015, 10am

MSE Building, G021

Advisor: Todd McDevitt, PhD, School of Biomedical Engineering

Committee:

Andrés García, PhD  School of Mechanical Engineering
Luke Brewster,MD/ PhD, Emory University School of Medicine

Title: Delivery of Prolyl Hydroxylase inhibitors to MSC Spheroids for Enhanced Angiogenesis.

Chronic non-healing wounds are a major healthcare concern in the U.S, especially due to the growing diabetic and elderly population. Wound healing is a complex biological process that is dependent on cells at the site of injury to signal and recruit immune cells, fibroblasts, and endothelial cells in order to rebuild damaged vasculature via angiogenesis. MSCs aid in wound healing and revascularization of damaged tissue because of their ability to secrete pro-angiogenic cytokines such as VEGF and IL-6 and recruit immune cells and endothelial cells to the site of injury to form new blood vessels. Hypoxia is known to be a key regulator in the angiogenic response of many cells, including MSCs.  Small molecule drugs termed Prolyl Hydroxylase inhibitors (PHDi) are able to cause a hypoxic response in cells can enhance MSCs ability to facilitate angiogenesis. The objective of this project is to investigate and compare the effects of commercially available PHDi on pro-angiogenic factor secretion of MSCs. Additionally, since the response to the drugs is likely short-lived, a method for prolonged delivery or exposure of PHDi to MSCs will be investigated.