Embryonic Stem Cell–Derived Cardiac Myocytes Are Not Ready for Human Trials
Human Embryonic-Stem-Cell-Derived Cardiomyocytes Regenerate Non-Human Primate Hearts Chong et al Nature. 2014;510:273–277.
Recently, a preclinical report assessed the efficacy, safety, and feasibility of using human embryonic stem cells to regenerate infarcted myocardium in a nonhuman primate model. This commentary evaluates that study by pointing out key weaknesses, offering an alternative perspective, and summarizing major unresolved issues. Our conclusion is that significant challenges remain before human embryonic stem cells are ready for use in clinical trials.
Ischemic heart disease (IHD) affects millions of patients. The cardiac dysfunction that results from IHD is secondary to the death of cardiac muscle cells. Current IHD treatments are inadequate, and there is a need to develop novel therapies to improve the lives of affected patients. New cellular therapies are being developed for repairing damaged hearts via induction of cardiac myocyte regeneration. In our view, approaches that can regenerate new, functional myocardium need to be tested first in small animal models and then in appropriate large animal models. Those approaches that are shown to be safe and to improve cardiac function in preclinical studies should then be considered for clinical application.
In a recent report in Nature, Chong et al1 describe experiments designed to test the potential of human embryonic stem cell–derived cardiac myocytes (hESC-CMs) to regenerate infarcted myocardium in a nonhuman primate model. This study was proposed by the authors as proof of concept for trials of these cells in patients. Our commentary looks at this report with an eye toward safety and efficacy of hESC-CMs.
A major advance in the study of Chong et al1 is that an approach has been developed to produce large quantities of hESC-CMs that seem to be sufficient for future use in humans with IHD. The authors were able to amplify 1 billion hESC-CMs, a number purported sufficient to regenerate an adult human infarcted heart. This approach addresses …