Preety Shakya

PhD Thesis Proposal Presentation

Date: Thursday, Aug 5, 2021
Time: 1pm - 3pm (EST)
Meeting Link:

https://emory.zoom.us/j/97826740215
Meeting ID: 978 2674 0215

Thesis Advisor: Dr. Michael E. Davis
Thesis Committee:

Dr. Chunhui Xu
Dr. Karen L. Christman
Dr. Rebecca D. Levit
Dr. Vahid Serpooshan

Title: 

Encapsulation of Pediatric Cardiac-derived C-kit+ Cells in Myocardial Extracellular Matrix Hydrogel for Cardiac Repair 

Abstract:

Hypoplastic Left Heart Syndrome (HLHS) is a critical congenital heart disease characterized by underdeveloped left side of the heart that occurs in 1 out of every 4000 births in the US. Despite aggressive palliative operations, clinical complications of right ventricle (RV) load bearing inevitably lead to RV failure, requiring transplantation. Pediatric cardiac-derived c-kit+ progenitor cells (CPCs) has shown potential for cardiac repair in recent studies through release of reparative factors and offer multiple benefits, such as easy isolation and autologous transplant. However, concerns about failure of engraftment and transient paracrine effects have thus far limited their use. To overcome these issues, an appropriate cell delivery vehicle such as a cardiac extracellular matrix (cECM) hydrogel can be utilized. This naturally derived biomaterial has demonstrated promising improvements in cardiac function in animal models and can provide healthy biochemical cues to CPCs allowing for local diffusion of therapeutic paracrine factors over time. The proposed study focuses on investigating an injectable, minimally invasive dual therapy that combines human CPCs and porcine cECM hydrogel to repair RV myocardium in HLHS patients. In this study, the effect of CPC encapsulation in cECM hydrogel on CPC functionality will be analyzed by looking at cellular differentiation, proliferation, and paracrine release in vitro. Intramyocardial injection of CPCs with cECM hydrogel will be performed in a rat RV failure model to assess improvements in RV function. Lastly, computational studies will be used to identify the underlying mechanism behind any pro-regenerative effects observed in vivo. The overall goal of this project is to obtain data for preclinical studies and accelerate the therapy towards clinical translation to treat RV dysfunction in HLHS patients.