Advancing in vitro models of human cardiac fibrosis: Manipulating mechanotransduction

Abstract

This thesis underscores the relevance of mechanobiology in cardiac fibrosis. A better understanding of the cardiac fibroblast’s microenvironment is essential to elucidate the disease mechanisms of cardiac fibrosis and to identify therapeutic targets. Combining tissue engineering techniques with organ-on-chip technology, advanced in vitro models offer the opportunity to accurately control both biochemical and mechanical stimuli, and to study their effects on cardiac fibroblast behavior, exemplified in this thesis by the demonstration of the antifibrotic effect of cyclic strain. Moreover, advanced in vitro models can serve as physiologically relevant drug testing platforms, as illustrated in our research by the identification of the antifibrotic effects of cardiac cell therapy and pirfenidone. Overall, the work presented in this thesis stresses the importance of taking mechanobiology and the cardiac fibroblast’s microenvironment into account in future cardiac fibrosis research.