Investigating Mechanisms Leading to Ventricular Tachycardia Following Cardiac Stem Cell Injections

Abstract

This dissertation discusses the use of computational models to understand possible mechanisms leading to ventricular tachycardia (VT) following cardiac regenerative therapies. We review the history of cardiac stem cell therapies and the current challenges being faced in Chapter 1. Particular emphasis is given to how computational models are a valuable tool for understanding VT mechanisms. Chapter 2 tests the hypothesis that VT following stem cell therapy can be explained by the evolution of graft-host coupling over time in novel computational slice models. These models are derived from 2D histology images of non-human primates that provide a realistic look at engrafted cell geometry. Chapter 3 explores how individual grafts and groups of grafts can affect arrhythmogenicity and looks at spatial parameters that may be important for future injection strategies. Chapter 4 examines how modulation of the intrinsic beating rate of stem cell-derived cardiomyocytes affects focal VT in three in silico human slice models. The work presented in this dissertation provides valuable insights into VT mechanisms and new toolsets that can be used to generate and test hypotheses that can be used by experimentalists and computational modelers alike.