Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate Non-Human Primate Hearts
By J. Chong, Xiulan Yang, C. Don, E. Minami, Yen-Wen Liu, Jill J. Weyers, W. M. Mahoney, Benjamin Van Biber, Savannah M. Cook, N. Palpant and 15 more. Nature, 2014
1,342 citations recorded by the source corpus.
Pluripotent stem cells provide a potential solution to current epidemic rates of heart failure by providing human cardiomyocytes to support heart regeneration. Studies of human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) in small-animal models have shown favourable effects of this treatment. However, it remains unknown whether clinical-scale hESC-CM transplantation is feasible, safe or can provide sufficient myocardial regeneration. Here we show that hESC-CMs can be produced at a clinical scale (more than one billion cells per batch) and cryopreserved with good viability. Using a non-human primate model of myocardial ischaemia followed by reperfusion, we show that cryopreservation and intra-myocardial delivery of one billion hESC-CMs generates extensive remuscularization of the infarcted heart. The hESC-CMs showed progressive but incomplete maturation over a 3-month period. Grafts were perfused by host vasculature, and electromechanical junctions between graft and host myocytes were present within 2 weeks of engraftment. Importantly, grafts showed regular calcium transients that were synchronized to the host electrocardiogram, indicating electromechanical coupling. In contrast to small-animal models, non-fatal ventricular arrhythmias were observed in hESC-CM-engrafted primates. Thus, hESC-CMs can remuscularize substantial amounts of the infarcted monkey heart. Comparable remuscularization of a human heart should be possible, but potential arrhythmic complications need to be overcome.
Subfields: Molecular Biology, Surgery
View Paper: https://www.semanticscholar.org/paper/98dbcdef0ba7e65242e6e608d26031cbdb51ad34
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Citations in the corpus
- Embryonic Stem Cell-Derived Exosomes Promote Endogenous Repair Mechanisms and Enhance Cardiac Function Following Myocardial Infarction (2015, background): “failure, however, this also has been reported to enhance arrhythmogenic response.(12,13) In spite of their impressive cardiac repair ability, teratoma formation has been observed(14,15) after transplantation of an unpurified ESC-derived cardiomyocyte population.”
- Pathophysiology of Myocardial Infarction (2015, positive): “tial for cardiomyocyte differentiation and may prove effective in promoting cardiac regeneration following infarction (58, 212).”
- Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development (2015, methodology): “The differentiation setup was initiated by plating undifferentiated human ESCs as single cells as described previously [50 – 52].”