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

Abstract：

: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.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

Bargehr J,Ong LP,Colzani M,Davaapil H,Hofsteen P,Bhandari S,Gambardella L,Le Novère N,Iyer D,Sampaziotis F,Weinberger F,Bertero A,Leonard A,Bernard WG,Martinson A,Figg N,Regnier M,Bennett MR,Murry CE,Sinha S

doi

10.1038/s41587-019-0197-9

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

895-906

issue

8

eissn

1087-0156

issn

1546-1696

pii

10.1038/s41587-019-0197-9

journal_volume

37

pub_type

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