Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts

Shiba, Yuji, Fernandes, Sarah, Zhu, Wei-Zhong, Filice, Dominic, Muskheli, Veronica, Kim, Jonathan, Palpant, Nathan J., Gantz, Jay, Moyes, Kara W., Reinecke, Hans, Van Biber, Benjamin, Dardas, Todd, Mignone, John L., Izawa, Atsushi, Hanna, Ramy, Viswanathan, Mohan, Gold, Joseph D., Kotlikoff, Michael I., Sarvazyan, Narine, Kay, Matthew W., Murry, Charles E. and Laflamme, Michael A. (2012) Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts. Nature, 489 7415: 322-325. doi:10.1038/nature11317

Author Shiba, Yuji
Fernandes, Sarah
Zhu, Wei-Zhong
Filice, Dominic
Muskheli, Veronica
Kim, Jonathan
Palpant, Nathan J.
Gantz, Jay
Moyes, Kara W.
Reinecke, Hans
Van Biber, Benjamin
Dardas, Todd
Mignone, John L.
Izawa, Atsushi
Hanna, Ramy
Viswanathan, Mohan
Gold, Joseph D.
Kotlikoff, Michael I.
Sarvazyan, Narine
Kay, Matthew W.
Murry, Charles E.
Laflamme, Michael A.
Title Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
Publication date 2012-09-13
Year available 2012
Sub-type Article (original research)
DOI 10.1038/nature11317
Open Access Status Not yet assessed
Volume 489
Issue 7415
Start page 322
End page 325
Total pages 4
Place of publication United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1000 General
Abstract Transplantation studies in mice and rats have shown that human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) can improve the function of infarcted hearts, but two critical issues related to their electrophysiological behaviour in vivo remain unresolved. First, the risk of arrhythmias following hESC-CM transplantation in injured hearts has not been determined. Second, the electromechanical integration of hESC-CMs in injured hearts has not been demonstrated, so it is unclear whether these cells improve contractile function directly through addition of new force-generating units. Here we use a guinea-pig model to show that hESC-CM grafts in injured hearts protect against arrhythmias and can contract synchronously with host muscle. Injured hearts with hESC-CM grafts show improved mechanical function and a significantly reduced incidence of both spontaneous and induced ventricular tachycardia. To assess the activity of hESC-CM grafts in vivo, we transplanted hESC-CMs expressing the genetically encoded calcium sensor, GCaMP3 (refs 4, 5). By correlating the GCaMP3 fluorescent signal with the host ECG, we found that grafts in uninjured hearts have consistent 1:1 host-graft coupling. Grafts in injured hearts are more heterogeneous and typically include both coupled and uncoupled regions. Thus, human myocardial grafts meet physiological criteria for true heart regeneration, providing support for the continued development of hESC-based cardiac therapies for both mechanical and electrical repair.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID K08-HL80431
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 286 times in Thomson Reuters Web of Science Article | Citations
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