2024 Theses Doctoral

Engineering Models of the Human Myocardium for the Investigation of Cardiac Injury and Disease

Nash, Trevor Ray

Cardiovascular disease is the leading cause of death in the United States and the world. Progress in the development of new therapeutic strategies is hindered by shortcomings in our understanding of human myocardial pathophysiology and limitations in the ability of preclinical models to accurately predict successful clinical translation. The development of engineered models of the myocardium comprised of human cells derived from induced pluripotent stem cells has emerged as a promising strategy to overcome these problems.

This dissertation builds on this work by developing a new engineered cardiac tissue platform and then utilizing it to investigate three distinct myocardial pathologies: (1) genetic restrictive cardiomyopathy, (2) autoimmune mediated myocardial injury, and (3) myocardial ischemia and reperfusion injury. Results from these studies provide new insights into therapeutic strategies for the first two conditions and describe substantial progress towards the creation of an innovative model of the third.