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Nat Biotechnol. 2018 Aug;36(7):597-605. doi: 10.1038/nbt.4162. Epub 2018 Jul 2.

Human embryonic stem cell-derived cardiomyocytes restore function in infarcted hearts of non-human primates.

Author information

1
Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington, USA.
2
Center for Cardiovascular Biology, University of Washington, Seattle, Washington, USA.
3
Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
4
Department of Medicine/Cardiology, University of Washington, Seattle, Washington, USA.
5
Department of Pathology, University of Washington, Seattle, Washington, USA.
6
City of Hope, Beckman Research Institute, Duarte, California, USA.
7
Washington National Primate Research Center, University of Washington, Seattle, Washington, USA.
8
Department of Pediatrics, University of Washington, Seattle Children's Hospital, Seattle, Washington, USA.
9
Department of Radiology, University of Washington, Seattle, Washington, USA.
10
Research Institute of Biology and Biophysics, National Research Tomsk State University, Tomsk, Russia.
11
Department of Bioengineering, University of Washington, Seattle, Washington, USA.

Abstract

Pluripotent stem cell-derived cardiomyocyte grafts can remuscularize substantial amounts of infarcted myocardium and beat in synchrony with the heart, but in some settings cause ventricular arrhythmias. It is unknown whether human cardiomyocytes can restore cardiac function in a physiologically relevant large animal model. Here we show that transplantation of ∼750 million cryopreserved human embryonic stem cell-derived cardiomyocytes (hESC-CMs) enhances cardiac function in macaque monkeys with large myocardial infarctions. One month after hESC-CM transplantation, global left ventricular ejection fraction improved 10.6 ± 0.9% vs. 2.5 ± 0.8% in controls, and by 3 months there was an additional 12.4% improvement in treated vs. a 3.5% decline in controls. Grafts averaged 11.6% of infarct size, formed electromechanical junctions with the host heart, and by 3 months contained ∼99% ventricular myocytes. A subset of animals experienced graft-associated ventricular arrhythmias, shown by electrical mapping to originate from a point-source acting as an ectopic pacemaker. Our data demonstrate that remuscularization of the infarcted macaque heart with human myocardium provides durable improvement in left ventricular function.

PMID:
29969440
PMCID:
PMC6329375
DOI:
10.1038/nbt.4162
[Indexed for MEDLINE]
Free PMC Article

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