Human embryonic stem cell–derived cardiomyocytes restore function in infarcted hearts of non-human primates

597 Heart disease kills more people worldwide than any other illness1. Much of this morbidity and mortality occurs because the heart is one of the least regenerative organs in the human body2. The ability of cardiomyocytes to proliferate is limited to ~1% per year3–5, and it has been difficult to identify a cardiac stem cell population that can give rise to new myocytes at significant levels3,6. As a result, cardiac injuries, such as myocardial infarctions, heal by scar formation, and the heart loses contractile ability in direct relation to the muscle deficit. When significant myocardial mass is lost, patients often progress to heart failure. Drug treatments for heart failure manage symptoms but do not address the root problem of muscle deficiency. Over the last 20 years, there have been extensive efforts to induce the heart to heal by muscle regeneration rather than scarring7–9. Progress is being made on multiple fronts, including inducing cardiomyocyte proliferation10–15 and reprogramming fibroblasts into cardiomyocytes16–18. Here we focus on transplantation of human cardiomyocytes derived from hESCs. These early-stage cardiomyocytes survive after transplantation and form new, maturing myocardium in animal models of myocardial infarction19,20. They improve cardiac function when transplanted into the mouse21, rat22,23, and guinea pig24 infarct. A recent study from our group showed that hESC-CMs could remuscularize the infarcted hearts of macaque monkeys, where they formed electromechanical junctions with the host heart and beat in synchrony25. Although small-animal studies showed no evidence for arrhythmias, in monkeys hESC-CMs caused a transient period of ventricular arrhythmias25. Similar ventricular arrhythmias were reported when monkey pluripotent stem cell–derived cardiomyocytes were transplanted into infarcted monkey hearts26. The current study aimed to address two principal gaps in knowledge. The first was to learn whether hESC-CMs could restore Human embryonic stem cell–derived cardiomyocytes restore function in infarcted hearts of non-human primates

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