Cardiac Cell Therapy in Nonhuman Primates
A Significant Step Toward Clinical Translation
The human heart has a limited capacity for regeneration after injury. Cardiac cell therapy aims to repair the injured heart by replacing dead and damaged cells with de novo cardiomyocytes. Human pluripotent stem cells (from embryonic or induced pluripotent linages) represent an ideal source of cardiomyocytes and have been extensively studied in this context. Several preclinical studies in small animal models have shown that these stem cell–derived cardiomyocytes can electrically couple with the host myocardium and improve cardiac function.1 However, it is unclear whether promising findings in small animal models can be reproduced in large animal models, which have a heart size and heart rate closer to that of a human. In this study, Chong et al2 examine whether exogenously delivered human embryonic stem cell–derived cardiomyocytes (hESC-CMs) will engraft and electrically integrate with the host myocardium in a nonhuman primate model of myocardial infarction (MI).
How Was the Hypothesis Tested?
To determine whether cardiomyocytes could be transplanted on a large scale, the authors conducted preliminary experiments in a mouse model of MI to test whether cryopreserved hESC-CMs could engraft to damaged mouse myocardium as efficiently as noncryopreserved hESC-CMs. Subsequently, large numbers of hESC-CMs were generated from human embryonic stem cell lines and cryopreserved. Specifically, the authors used embryonic stem cell lines that had been genetically modified to express the fluorescent calcium indicator, green fluorescent protein/calmodulin/MB fusion protein 3. This enabled them to monitor calcium fluxes …