Biosensor-based profiling to track cellular signalling in patient-derived models of dilated cardiomyopathy

Abstract

Dilated cardiomyopathies (DCM) represent a diverse group of cardiovascular diseases impacting the structure and function of the myocardium. To better treat these diseases, we need to understand the impact of such cardiomyopathies on critical signalling pathways that drive disease progression downstream of receptors we often target therapeutically. Our understanding of cellular signalling events has progressed substantially in the last few years, in large part due to the design, validation and use of biosensor-based approaches to studying such events in cells, tissues and in some cases, living animals. Another transformative development has been the use of human induced pluripotent stem cells (hiPSCs) to generate disease-relevant models from individual patients. We highlight the importance of going beyond monocellular cultures to incorporate the influence of paracrine signalling mediators. Finally, we discuss the recent coalition of these approaches in the context of DCM. We discuss recent work in generating patient-derived models of cardiomyopathies and the utility of using signalling biosensors to track disease progression and test potential therapeutic strategies that can be later used to inform treatment options in patients.

Keywords: Biosensors; Cardiomyocytes; Cellular signalling; Dilated cardiomyopathy (DCM); Fibroblasts; Maturation; hiPSCs.