Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration

被引：143

作者：

Bargehr, Johannes ^{[1
,2
]}

Ong, Lay Ping ^{[1
,2
]}

Colzani, Maria ^{[1
,2
]}

Davaapil, Hongorzul ^{[1
,2
]}

Hofsteen, Peter ^{[3
]}

Bhandari, Shiv ^{[3
]}

Gambardella, Laure ^{[1
,2
]}

Le Novere, Nicolas ^{[4
]}

Iyer, Dharini ^{[1
,2
]}

Sampaziotis, Fotios ^{[1
]}

Weinberger, Florian ^{[3
]}

Bertero, Alessandro ^{[3
]}

Leonard, Andrea ^{[3
]}

Bernard, William G. ^{[1
,2
]}

Martinson, Amy ^{[3
]}

Figg, Nichola ^{[2
]}

Regnier, Michael ^{[5
]}

Bennett, Martin R. ^{[2
]}

Murry, Charles E. ^{[3
,5
,6
]}

Sinha, Sanjay ^{[1
,2
]}

机构：

[1] Univ Cambridge, Wellcome Trust MRC Cambridge Stem Cell Inst, Anne McLaren Lab, Cambridge, England

[2] Univ Cambridge, Div Cardiovasc Med, Cambridge, England

[3] Univ Washington, Dept Pathol, Ctr Cardiovasc Biol, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USA

[4] Babraham Inst, Cambridge, England

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

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

来源：

NATURE BIOTECHNOLOGY | 2019年 / 37卷 / 08期

基金：

英国医学研究理事会; 英国生物技术与生命科学研究理事会; 美国国家卫生研究院; 英国惠康基金;

关键词：

SMOOTH-MUSCLE-CELLS; EMBRYOLOGICAL ORIGIN; NEURAL CREST; GENERATION; EXPRESSION; INJURY; DIFFERENTIATION; TRANSPLANTATION; FIBROBLASTS; MYOCARDIUM;

D O I：

10.1038/s41587-019-0197-9

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：

The epicardium and its derivatives provide trophic and structural support for the developing and adult heart. Here we tested the ability of human embryonic stem cell (hESC)-derived epicardium to augment the structure and function of engineered heart tissue in vitro and to improve efficacy of hESC-cardiomyocyte grafts in infarcted athymic rat hearts. Epicardial cells markedly enhanced the contractility, myofibril structure and calcium handling of human engineered heart tissues, while reducing passive stiffness compared with mesenchymal stromal cells. Transplanted epicardial cells formed persistent fibroblast grafts in infarcted hearts. Cotransplantation of hESC-derived epicardial cells and cardiomyocytes doubled graft cardiomyocyte proliferation rates in vivo, resulting in 2.6-fold greater cardiac graft size and simultaneously augmenting graft and host vascularization. Notably, cotransplantation improved systolic function compared with hearts receiving either cardiomyocytes alone, epicardial cells alone or vehicle. The ability of epicardial cells to enhance cardiac graft size and function makes them a promising adjuvant therapeutic for cardiac repair.

引用

页码：895 / +

页数：15

共 59 条

[1] Embryological Origin of Human Smooth Muscle Cells Influences Their Ability to Support Endothelial Network Formation [J].