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

Sci Transl Med. 2016 Nov 2;8(363):363ra148. doi: 10.1126/scitranslmed.aaf8781.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiac Surgical Procedures*
  • Cell Differentiation
  • Cell Proliferation
  • Cicatrix
  • Echocardiography
  • Female
  • Guinea Pigs
  • Heart / physiology*
  • Heart Ventricles
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Lung / metabolism
  • Myocardium / pathology
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / transplantation
  • Regeneration
  • Spleen / metabolism
  • Tissue Engineering / methods*