Cardiac repair in guinea pigs with human engineered heart tissue from induced pluripotent stem cells
| Autor: | Florian Weinberger, Katrin Lessmann, Arne Hansen, Kai-Hung Cheng, Jutta Starbatty, K. Breckwoldt, Simon Pecha, Tomas Stølen, Birgit Geertz, Godfrey L. Smith, Thomas Eschenhagen, Marielle Scherrer-Crosbie, Timur A. Yorgan, Allen Kelly, Hermann Reichenspurner |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Cellular differentiation Heart Ventricles Guinea Pigs Induced Pluripotent Stem Cells Guinea pig 03 medical and health sciences Cicatrix Tissue engineering medicine Animals Humans Regeneration Myocytes Cardiac Cardiac Surgical Procedures Induced pluripotent stem cell Lung Cell Proliferation Tissue Engineering business.industry Regeneration (biology) Myocardium Cell Differentiation Heart General Medicine Anatomy Transplantation Endothelial stem cell 030104 developmental biology medicine.anatomical_structure Echocardiography Female business Spleen |
| Zdroj: | Science translational medicine. 8(363) |
| ISSN: | 1946-6242 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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