Electromechanical integration of cardiomyocytes derived from human embryonic stem cells

Nat Biotechnol. 2004 Oct;22(10):1282-9. doi: 10.1038/nbt1014. Epub 2004 Sep 26.


Cell therapy is emerging as a promising strategy for myocardial repair. This approach is hampered, however, by the lack of sources for human cardiac tissue and by the absence of direct evidence for functional integration of donor cells into host tissues. Here we investigate whether cells derived from human embryonic stem (hES) cells can restore myocardial electromechanical properties. Cardiomyocyte cell grafts were generated from hES cells in vitro using the embryoid body differentiating system. This tissue formed structural and electromechanical connections with cultured rat cardiomyocytes. In vivo integration was shown in a large-animal model of slow heart rate. The transplanted hES cell-derived cardiomyocytes paced the hearts of swine with complete atrioventricular block, as assessed by detailed three-dimensional electrophysiological mapping and histopathological examination. These results demonstrate the potential of hES-cell cardiomyocytes to act as a rate-responsive biological pacemaker and for future myocardial regeneration strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Body Surface Potential Mapping
  • Cardiac Pacing, Artificial / methods*
  • Cell Differentiation
  • Graft Survival
  • Heart Block / diagnosis
  • Heart Block / physiopathology*
  • Heart Block / surgery*
  • Heart Conduction System / physiopathology*
  • Humans
  • Myocardial Contraction*
  • Myocytes, Cardiac*
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cell Transplantation / methods*
  • Swine
  • Treatment Outcome