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

被引：464

作者：

Liu, Yen-Wen ^{[1
,2
,3
]}

Chen, Billy ^{[1
,2
,4
]}

Yang, Xiulan ^{[1
,2
,5
]}

Fugate, James A. ^{[1
,2
,5
]}

Kalucki, Faith A. ^{[1
,2
,5
]}

Futakuchi-Tsuchida, Akiko ^{[1
,2
,5
]}

Couture, Larry ^{[6
,12
]}

Vogel, Keith W. ^{[7
]}

Astley, Clifford A. ^{[7
]}

Baldessari, Audrey ^{[7
]}

Ogle, Jason ^{[7
]}

Don, Creighton W. ^{[4
]}

Steinberg, Zachary L. ^{[4
]}

Seslar, Stephen P. ^{[4
,8
]}

Tuck, Stephanie A. ^{[1
,2
,5
,13
]}

Tsuchida, Hiroshi ^{[1
,2
,5
]}

Naumova, Anna V. ^{[1
,2
,9
,10
]}

Dupras, Sarah K. ^{[1
,2
,5
]}

Lyu, Milly S. ^{[9
]}

Lee, James ^{[4
]}

Hailey, Dale W. ^{[1
]}

Reinecke, Hans ^{[1
,2
,5
]}

Pabon, Lil ^{[1
,2
,5
]}

Fryer, Benjamin H. ^{[1
,2
,5
]}

MacLellan, W. Robb ^{[1
,2
,4
]}

Thies, R. Scott ^{[1
,2
,5
]}

Murry, Charles E. ^{[1
,2
,4
,5
,11
]}

机构：

[1] Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USA

[2] Univ Washington, Ctr Cardiovasc Biol, Seattle, WA 98195 USA

[3] Natl Cheng Kung Univ Hosp, Natl Cheng Kung Univ, Coll Med, Div Cardiol,Dept Internal Med, Tainan, Taiwan

[4] Univ Washington, Dept Med Cardiol, Seattle, WA 98195 USA

[5] Univ Washington, Dept Pathol, Seattle, WA 98195 USA

[6] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA USA

[7] Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA

[8] Univ Washington, Dept Pediat, Seattle Childrens Hosp, Seattle, WA 98195 USA

[9] Univ Washington, Dept Radiol, Seattle, WA 98195 USA

[10] Natl Res Tomsk State Univ, Res Inst Biol & Biophys, Tomsk, Russia

[11] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA

[12] Natl Univ Ireland Galway, Orbsen Therapeut LTD, Orbsen Bldg, Galway, Ireland

[13] Uptake Med Technol, Seattle, WA USA

来源：

NATURE BIOTECHNOLOGY | 2018年 / 36卷 / 07期

关键词：

MYOCARDIAL-INFARCTION; REGENERATIVE MEDICINE; RAT HEARTS; CARDIAC REGENERATION; PROARRHYTHMIC RISK; TRANSPLANTATION; DIFFERENTIATION; MATURATION; ARRHYTHMIAS; MYOCYTES;

D O I：

10.1038/nbt.4162

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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 similar to 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 similar to 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.

引用

页码：597 / +

页数：13

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