Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate the Infarcted Pig Heart but Induce Ventricular Tachyarrhythmias

被引：204

作者：

Romagnuolo, Rocco ^{[1
]}

Masoudpour, Hassan ^{[1
]}

Porta-Sanchez, Andreu ^{[2
]}

Qiang, Beiping ^{[1
]}

Barry, Jennifer ^{[3
]}

Laskary, Andrew ^{[1
]}

Qi, Xiuling ^{[3
]}

Masse, Stephane ^{[2
]}

Magtibay, Karl ^{[2
]}

Kawajiri, Hiroyuki ^{[4
]}

Wu, Jun ^{[4
]}

Sadikov, Tamilla Valdman ^{[1
]}

Rothberg, Janet ^{[5
]}

Panchalingam, Krishna M. ^{[5
]}

Titus, Emily ^{[5
]}

Li, Ren-Ke ^{[2
,4
,6
]}

Zandstra, Peter W. ^{[5
,6
]}

Wright, Graham A. ^{[3
,6
]}

Nanthakumar, Kumaraswamy ^{[2
,6
]}

Ghugre, Nilesh R. ^{[3
,6
]}

Keller, Gordon ^{[1
,6
]}

Laflamme, Michael A. ^{[1
,2
,6
]}

机构：

[1] Univ Hlth Network, McEwen Stem Cell Inst, Toronto, ON M5G 1L7, Canada

[2] Univ Hlth Network, Peter Munk Cardiac Ctr, Toronto, ON M5G 2N2, Canada

[3] Sunnybrook Hlth Sci Ctr, Schulich Heart Res Program, Toronto, ON M4N 3M5, Canada

[4] Univ Hlth Network, Toronto Gen Hosp Res Inst, Toronto, ON M5G 1L7, Canada

[5] Ctr Commercializat Regenerat Med, Toronto, ON M5G 1M1, Canada

[6] Univ Toronto, Toronto, ON M5G 1L7, Canada

来源：

STEM CELL REPORTS | 2019年 / 12卷 / 05期

基金：

加拿大创新基金会;

关键词：

CARDIOVASCULAR PROGENITORS; TRANSPLANTATION; THERAPY;

D O I：

10.1016/j.stemcr.2019.04.005

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) show considerable promise for regenerating injured hearts, and we therefore tested their capacity to stably engraft in a translationally relevant preclinical model, the infarcted pig heart. Transplantation of immature hESC-CMs resulted in substantial myocardial implants within the infarct scar that matured over time, formed vascular networks with the host, and evoked minimal cellular rejection. While arrhythmias were rare in infarcted pigs receiving vehicle alone, hESC-CM recipients experienced frequent monomorphic ventricular tachycardia before reverting back to normal sinus rhythm by 4 weeks post transplantation. Electroanatomical mapping and pacing studies implicated focal mechanisms, rather than macro-reentry, for these graft-related tachyarrhythmias as evidenced by an abnormal centrifugal pattern with earliest electrical activation in histologically confirmed graft tissue. These findings demonstrate the suitability of the pig model for the preclinical development of a hESC-based cardiac therapy and provide new insights into the mechanistic basis of electrical instability following hESC-CM transplantation.

引用

页码：967 / 981

页数：15

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