EP News: Basic and Translational

Abstract

Stem cell transplantation studies in mice and rats have shown that human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) can improve the function of infarcted hearts. However, there are 2 unresolved issues related to their electrophysiological behavior in vivo. First, the risk of arrhythmias following hESC-CM transplantation in injured hearts has not been determined. Second, the electromechanical integration of hESC-CMs in injured hearts has not been demonstrated, so it is unclear whether these cells improve contractile function directly through addition of new force-generating units. Shiba et al (Nature. 2012;489:322, PMID 22864415) used a guinea pig model to show that hESC-CM grafts in injured hearts protect against arrhythmias and can contract synchronously with host muscle. Injured hearts with hESC-CM grafts show improved mechanical function and a significantly reduced incidence of both spontaneous and induced ventricular tachycardia. To assess the activity of hESC-CM grafts in vivo, the authors transplanted hESC-CMs expressing a genetically encoded calcium sensor. By correlating the sensor's fluorescent signals with the host ECG, they found that grafts in uninjured hearts have consistent 1:1 host-graft coupling. Grafts in injured hearts are more heterogeneous and typically include both coupled and uncoupled regions. These findings show that human cardiomyocytes can integrate and contract synchronously with the host myocardium. The authors conclude that human myocardial grafts meet physiological criteria for true heart regeneration, providing support for the continued development of hESC-based cardiac therapies for both mechanical and electrical repair.