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Sci Transl Med. 2016 Nov 2;8(363):363ra148.

Cardiac repair in guinea pigs with human engineered heart tissue from induced pluripotent stem cells.

Author information

1
Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
2
German Centre for Cardiovascular Research (DZHK), partner site Hamburg/Kiel/L├╝beck, Germany.
3
Department of Cardiovascular Surgery, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
4
K.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, 7030 Trondheim, Norway.
5
Norwegian Council on Cardiovascular Disease, Oslo, Norway.
6
Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
7
Cardiac Ultrasound Laboratory, Massachusetts General Hospital, Boston, MA 02114, USA.
8
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, UK.
9
Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. t.eschenhagen@uke.de.

Abstract

Myocardial injury results in a loss of contractile tissue mass that, in the absence of efficient regeneration, is essentially irreversible. Transplantation of human pluripotent stem cell-derived cardiomyocytes has beneficial but variable effects. We created human engineered heart tissue (hEHT) strips from human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and hiPSC-derived endothelial cells. The hEHTs were transplanted onto large defects (22% of the left ventricular wall, 35% decline in left ventricular function) of guinea pig hearts 7 days after cryoinjury, and the results were compared with those obtained with human endothelial cell patches (hEETs) or cell-free patches. Twenty-eight days after transplantation, the hearts repaired with hEHT strips exhibited, within the scar, human heart muscle grafts, which had remuscularized 12% of the infarct area. These grafts showed cardiomyocyte proliferation, vascularization, and evidence for electrical coupling to the intact heart tissue in a subset of engrafted hearts. hEHT strips improved left ventricular function by 31% compared to that before implantation, whereas the hEET or cell-free patches had no effect. Together, our study demonstrates that three-dimensional human heart muscle constructs can repair the injured heart.

PMID:
27807283
DOI:
10.1126/scitranslmed.aaf8781
[Indexed for MEDLINE]

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