Human embryonic-stem-cell-derived cardiomyocytesregenerate non-humanprimate hearts

被引：1085

作者：

Chong, James J. H. ^{[1
,2
,3
,4
,5
]}

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

Don, Creighton W. ^{[6
]}

Minami, Elina ^{[1
,2
,5
,6
]}

Liu, Yen-Wen ^{[1
,2
,5
]}

Weyers, Jill J. ^{[1
,2
,5
]}

Mahoney, William M., Jr. ^{[1
,2
,5
]}

Van Biber, Benjamin ^{[1
,2
,5
]}

Cook, Savannah M. ^{[7
]}

Palpant, Nathan J. ^{[1
,2
,5
]}

Gantz, Jay A. ^{[1
,2
,5
,8
]}

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

Muskheli, Veronica ^{[1
,2
,5
]}

Gough, G. Michael ^{[9
]}

Vogel, Keith W. ^{[9
]}

Astley, Cliff A. ^{[9
]}

Hotchkiss, Charlotte E. ^{[9
]}

Baldessari, Audrey ^{[9
]}

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

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

Gill, Edward A. ^{[6
]}

Nelson, Veronica ^{[10
]}

Kiem, Hans-Peter ^{[5
,10
]}

Laflamme, Michael A. ^{[1
,2
,5
]}

Murry, Charles E. ^{[1
,2
,5
,6
,8
]}

机构：

[1] Univ Washington, Ctr Cardiovasc Biol, Seattle, WA 98109 USA

[2] Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98109 USA

[3] Westmead Hosp, Dept Cardiol, Westmead, NSW 2145, Australia

[4] Univ Sydney, Sch Med, Sydney, NSW 2006, Australia

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

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

[7] Univ Washington, Inst Stem Cell & Regenerat Med, Dept Comparat Med, Seattle, WA 98109 USA

[8] Univ Washington, Dept Bioengn, Seattle, WA 98109 USA

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

[10] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA

来源：

NATURE | 2014年 / 510卷 / 7504期

基金：

美国国家卫生研究院; 英国医学研究理事会;

关键词：

LARGE ANIMAL-MODELS; ENGRAFT;

D O I：

10.1038/nature13233

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Pluripotent stem cells provide a potential solution to current epidemic rates of heart failure(1) by providing human cardiomyocytes to support heart regeneration(2). Studies of human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) in small-animal models have shown favourable effects of this treatment(3-7). 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 intramyocardial delivery of one billion hESC-CMs generates extensive remuscularization of the infarctedheart. 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(7), nonfatal 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.

引用

页码：273 / +

页数：17

共 30 条

[1]

Composite Cell Sheets A Further Step Toward Safe and Effective Myocardial Regeneration by Cardiac Progenitors Derived From Embryonic Stem Cells [J].