Fluorescent PSC-Derived Cardiomyocyte Reporter Lines: Generation Approaches and Their Applications in Cardiovascular Medicine.

Abstract

Simple SummaryUnderstanding how heart muscle cells function and developing new strategies for repairing the damaged heart are important challenges for tackling heart disease. Human cells from the heart are required in the laboratory for these investigations, but are difficult to obtain in large numbers from patients. As an alternative, stem cells can be used which can be cultured indefinitely in the laboratory and then turned into heart muscle cells. The current methods lead to a mixture of cell types, belonging to the different regions of the heart, creating difficulties when trying to understand the biology of a particular area of the heart, or for future applications when these stem cell-derived cell types are used to repair the heart. Genetic modification of stem cells provides a solution to this problem, as these techniques allow fluorescent markers, so-called reporters, to be inserted into key genes that are active in the different cell types. The different coloured reporters thus allow the identification and purification of specific cell types. In this review, we discuss the various methods that can be used to establish these reporter systems and highlight their applications in different aspects of cardiovascular medicine.Recent advances have made pluripotent stem cell (PSC)-derived cardiomyocytes an attractive option to model both normal and diseased cardiac function at the single-cell level. However, in vitro differentiation yields heterogeneous populations of cardiomyocytes and other cell types, potentially confounding phenotypic analyses. Fluorescent PSC-derived cardiomyocyte reporter systems allow specific cell lineages to be labelled, facilitating cell isolation for downstream applications including drug testing, disease modelling and cardiac regeneration. In this review, the different genetic strategies used to generate such reporter lines are presented with an emphasis on their relative technical advantages and disadvantages. Next, we explore how the fluorescent reporter lines have provided insights into cardiac development and cardiomyocyte physiology. Finally, we discuss how exciting new approaches using PSC-derived cardiomyocyte reporter lines are contributing to progress in cardiac cell therapy with respect to both graft adaptation and clinical safety.