Maturation of Human Pluripotent Stem Cell–Derived Cardiomyocytes

In the past 6 years, multiple laboratories have reported the successful directed cardiomyocyte differentiation from human pluripotent stem cells (hPSCs; reviewed in Burridge et al). These stem cell–derived cardiomyocytes beat spontaneously, express the expected sarcomeric proteins and ion channels, and exhibit cardiac-type action potentials and calcium transients. They show similar functional properties to the cardiomyocytes in the developing heart with comparable excitation–contraction coupling (ECC) mechanism and neurohormonal signaling. After transplantation into infarcted hearts of mice, rats, and guinea pigs, hPSC cardiomyocytes (hPSC-CMs) engraft, form gap junctions with the host cardiomyocytes, reduce adverse remodeling, and enhance cardiac mechanical function. Despite these promising results, many lines of evidence indicate that under the conditions currently used, hPSC-CMs do not exhibit the morphological and functional characteristics of adult cardiomyocytes. Review