Electromechanical integration of cardiomyocytes derived from human embryonic stem cells

Izhak Kehat, Leonid Khimovich, Oren Caspi, Amira Gepstein, Rona Shofti, Gil Arbel, Irit Huber, Jonathan Satin, Joseph Itskovitz-Eldor, Lior Gepstein

Research output: Contribution to journalArticlepeer-review

754 Scopus citations


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.

Original languageEnglish
Pages (from-to)1282-1289
Number of pages8
JournalNature Biotechnology
Issue number10
StatePublished - Oct 2004

Bibliographical note

Funding Information:
We thank Asaf Zaretzki and Edith Cohen for their valuable help in the animal studies. We thank Ofer Shenker and the interdisciplinary unit for their technical assistance. This research was supported in part by the Israel Science Foundation (grant no. 520/01), by the Israel Health Ministry, by the Johnson & Johnson Focused Research Grant and by the Nahum Guzik Research Fund.

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering


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