Functional Properties of Human Embryonic Stem Cell−Derived Cardiomyocytes

Abstract

Cardiovascular diseases are the most frequent cause of death in the industrialized world, with the main contributor being myocardial infarction. Given the high morbidity and mortality rates associated with congestive heart failure, the shortage of donor hearts for transplantation, complications resulting from immunosuppression, and long-term failure of transplanted organs, regeneration of the diseased myocardium by cell transplantation is an attractive therapeutic modality. Because of their remarkable capacity for expansion and unquestioned cardiac potential, pluripotent human embryonic stem cells (hESC) represent an attractive candidate cell source for obtaining cardiomyocytes. Moreover, a number of recent reports have shown that hESC-derived cardiomyocytes (hESC-CM) survive after transplantation into infarcted rodent hearts, form stable cardiac implants, and result in preserved contractile function. Although the latter successes give good reason for optimism, considerable challenges remain in the successful application of hESC-CM to cardiac repair. Because it is desired that the transplanted cells fully integrate within the diseased myocardium, contribute to its contractile performance, and respond appropriately to various physiological stimuli, it is of crucial importance to be familiar with their functional properties. Therefore, this review describes the characteristics of hESC-CM, including their transcriptional profile, structural and electrophysiological properties, ion channel expression, excitation-contraction coupling, and neurohumoral responsiveness.