While self-renewable, pluripotent human (h) embryonic stem cells (ESCs) can provide an unlimited source of donor cardiomyocytes (CMs) for myocardial repair, we showed in a preclinical large (porcine) animal transplantation model that their cardiac derivatives with immature properties are prime substrates for lethal cardiac arrhythmias. To address this, we developed an approach for driven maturation of hESC-derived CMs (hESCCMs) that renders the cellular electrophysiological phenotype adult-like and thus completely ablates post-transplantation ventricular tachycardias (VT)/fibrillation (VF).

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