Engineering Stem Cell Responses using Oxidative Stress and Notch Ligand Containing Hydrogels

Advisor: Dr. Michael E Davis, Associate Professor, Emory University

Committee Members:
Dr. Andres Garcia, Department of Mechanical Engineering, Georgia Institute of Technology
Dr. Hanjoong Jo, Department of Medicine, Emory University
Dr. Manu Platt, Department of Biomedical Engineering, Georgia Institute of Technology
Dr. Khalid Salaita, Department of Chemistry, Emory University
 
Heart failure is the leading cause of death worldwide.   In 2013, the American Heart Association estimated that one American will die of cardiovascular disease every 39 seconds.  While heart transplantation is the most viable treatment option, the limited availability of donor hearts has necessitated the search for treatment alternatives such as the use of adult stem cells for cardiac repair and regeneration.  Following myocardial infarction (MI), the inflammatory cardiac microenvironment, limited survival of stem/progenitor cells, myocardial scarring and fibrosis affect cardiac regeneration.  This dissertation examines adult stem cell based approaches for cardiac regeneration by studying the effect of i) H2O2- mediated oxidative stress on mesenchymal stem cells, ii) Notch1 activation in cardiac progenitor cells using a self-assembling peptide hydrogel containing the Notch1 ligand mimic RJ in vitro and functional consequences in a rat model of MI.
            Through these approaches, the central hypothesis that modulation of stem cell response using cues such as oxidative stress and activation of Notch1 signaling can improve functional outcome following myocardial infarction has been studied.