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

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.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

Liu YW,Chen B,Yang X,Fugate JA,Kalucki FA,Futakuchi-Tsuchida A,Couture L,Vogel KW,Astley CA,Baldessari A,Ogle J,Don CW,Steinberg ZL,Seslar SP,Tuck SA,Tsuchida H,Naumova AV,Dupras SK,Lyu MS,Lee J,Hailey DW,Reinec

doi

10.1038/nbt.4162

subject

Has Abstract

pub_date

2018-08-01 00:00:00

pages

597-605

issue

7

eissn

1087-0156

issn

1546-1696

pii

nbt.4162

journal_volume

36

pub_type

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