The human embryonic stem cell-derived cardiomyocyte as a pharmacological model

Abstract

Embryonic stem (ES) cells are specialised cells derived from the early embryo, which are capable of both sustained propagation in the undifferentiated state as well as subsequent differentiation into the majority of cell lineages. Human ES cells are being developed for clinical tissue repair, but a number of problems must be addressed before this becomes a reality. However, they also have potential for translational benefit through its use as a test system for screening pharmaceutical compounds. In the cardiac field, present model systems are not ideal for either screening or basic pharmacological/physiological studies. Cardiomyocytes produced from human ES differentiation have advantages for these purposes over the primary isolated cells or the small number of cell lines available. This review describes the methodology for obtaining cardiomyocytes from human embryonic stem cell-derived cardiomyocyte (hESCM), for increasing the proportion of cardiomyocytes in the preparation and for isolating single embryonic stem cell-derived cardiomyocyte (ESCM) from clusters. Their morphological, contractile and electrophysiological characteristics are compared to mature and immature primary cardiomyocytes. The advantages and disadvantages of the hESCM preparation for long term culture and genetic manipulation are described. Basic pharmacological studies on adrenoceptors and muscarinic receptors in hESCM have been performed, and have given stable and reproducible responses. Prolongation of repolarisation can be detected using hESCM cultured on multielectrode arrays (MEA). Human ESCM have a clear potential to improve model systems available for both basic scientific studies and pharmaceutical screening of cardiac target compounds.