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

Weinberger, F. et al. (2016) Cardiac repair in guinea pigs with human engineered heart tissue from induced pluripotent stem cells. Science Translational Medicine, 8(363), 363ra148-363ra148. (doi:10.1126/scitranslmed.aaf8781) (PMID:27807283)

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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.

Item Type:Articles
Additional Information:This work was supported by the German Centre for Cardiovascular Research (DZHK; NCCR 3.1 HF for A.H. and T.E.), the German Ministry of Research and Education (BMBF), Deutsche Herzstiftung (F/36/12 for F.W. and T.E.), a European Research Council Advanced Grant (IndivuHeart for T.E.), the German Research Foundation (Es 88/12-1 for T.E.), and the European Union (EU FP7 Biodesign for T.E.).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Smith, Professor Godfrey and Kelly, Mr Allen
Authors: Weinberger, F., Breckwoldt, K., Pecha, S., Kelly, A., Geertz, B., Starbatty, J., Yorgan, T., Cheng, K.-H., Lessmann, K., Stolen, T., Scherrer-Crosbie, M., Smith, G., Reichenspurner, H., Hansen, A., and Eschenhagen, T.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Science Translational Medicine
Publisher:American Association for the Advancement of Science
ISSN:1946-6234
ISSN (Online):1946-6242

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