Understanding the electrophysiological maturation of human adult cardiomyocytes: lessons from the heart to be used for differentiation of pluripotent stem cells into cardiomyocytes

Abstract

The main focus of using human pluripotent stem cell derived cardiomyocytes (hPSC-CM) has long been on the field of regenerative medicine. The past decade the focus shifted towards using hPSC-CM as an in vitro model for screening of pro-arrhythmic compounds during drug development and to study cardiac arrhythmia-related diseases. The application of hPSC-CM as a new in vitro model requires a close resemblance between the physiology of hPSC-CM and human adult CM, especially regarding electrophysiology and contractility. We review the cardiac differentiation of hPSCs into CMs compared to the human fetal cardiac development. The comparison entails which transcription factors and signaling pathways are important in human cardiac development and applied in cardiac differentiation protocols. Moreover, electrophysiology and contractility of hPSC-CMs are compared with human adult CMs by evaluating gene expression and ion current recordings. An attempt is made to relate ion channel expression to transcription factors and signaling pathways expressed during human fetal cardiac development, to improve cardiac differentiation protocols producing more mature hPSC-CMs.