Multiple studies have shown that transplantation of embryonic stem cells (ESC) into failing or ischemic heart tissue is beneficial. The mechanisms behind such benefit may include paracrinal and angiogenic factors, as well as direct regeneration of a functional cardiac network from differentiating ESC. The main overall goal of the proposed studies is to understand how the engraftment of Embryonic Stem Cell-derived Cardiac Myocytes (ESC-CM) affects electrophysiological properties of the host cardiac tissue. The applicant will test a novel hypothesis that overexpression of N-cadherin, a key junctional protein, facilitates the incorporation of ESC-CM into the host cardiomyocyte network and alleviates ESC-CM arrhythmogenicity. The sponsor's lab has extensive experience in cardiac physiology. Recently they become interested in a regenerative potential of stem cells for repair of ischemic tissue, specifically mechanisms that can ensure safe and efficient ESC engraftment. En route to this goal, the methods of ESC culture and cardiac lineage commitment were successfully adapted, and in vitro model of ESC-cardiac muscle engraftment was developed. Working in the sponsor's lab will allow the PI to apply her previous expertise in molecular biology, while gaining knowledge and techniques that are used in stem cell research and cardiovascular physiology. This study and training opportunity will enrich the PI as a scientist and prepare her for an independent career. To assess the impulse propagation and excitability properties of cardiomyocyte networks enriched with ESC-CM. To address the occurrence and development of ectopic arrhythmias in the cardiomyocyte networks enriched with ESC-CM. To address the occurrence and pacing response of reentry waves in the cardiomyocyte networks engrafted with ESC-CM. To test the novel hypothesis that overexpression of N-cadherin will improve the electrical and mechanical connectivity of ESC-CM to the host myocardium, leading to decreased arrhythmogenicity of these cells.
| Karabekian, Zaruhi; Posnack, Nikki Gillum; Sarvazyan, Narine (2011) Immunological barriers to stem-cell based cardiac repair. Stem Cell Rev 7:315-25 |
| Gillum, Nikki; Karabekian, Zaruhi; Swift, Luther M et al. (2009) Clinically relevant concentrations of di (2-ethylhexyl) phthalate (DEHP) uncouple cardiac syncytium. Toxicol Appl Pharmacol 236:25-38 |
| Karabekian, Zaruhi; Gillum, Nikki D; Wong, Elissa W P et al. (2009) Effects of N-cadherin overexpression on the adhesion properties of embryonic stem cells. Cell Adh Migr 3:305-10 |
