David Trac

PhD Proposal Presentation

Date: September 20th, 2017

Time: 3:30pm

Location: Health Sciences Research Building E360

Committee Members:

Michael E. Davis, PhD (Advisor)

Chunhui Xu, PhD

Steven L. Goudy, MD

Luke P. Brewster, MD, PhD

Joshua T. Maxwell, PhD

Improving the Therapeutic Functionality of Child Cardiac Progenitor Cells by Spherical Aggregation

Cardiac stem cell therapies have been limited by low differentiation rates and many studies have shown that upwards of 90% of cells are lost within a few days post-transplantation. Moreover, cardiac progenitor cells lose their regenerative potential as they age, occurring as early as 1 year old. Based on these limitations, current autologous stem cell therapies for heart failure may not be as effective as they could be. The goal of this proposed project is to improve the therapeutic functionality of child (>1 year old) cardiac progenitor cells by aggregating them into scaffold-free spheres. The overall hypothesis is that the three-dimensional microenvironment may recapitulate signaling processes within the native cardiac stem cell niche, particularly Notch1. This signaling may improve the differentiation of child cardiac progenitor cells into mature cardiac phenotypes. Additionally, the effect of cardiac progenitor cell aggregation on exosome content will be investigated, as cardiac progenitor cell-derived exosomes have been shown to play a key role in cardioprotection. Finally, the ability of aggregated cardiac progenitor cells to improve cardiac function, compared to monolayer cultured cells, will be assessed in a rat right ventricular heart failure model.