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(Circulation Research. 2008;102:1008.)
© 2008 American Heart Association, Inc.

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Human Embryonic Stem Cell–Derived Cardiomyocytes and Cardiac Repair in Rodents

Linda W. van Laake, Robert Passier, Pieter A. Doevendans, Christine L. Mummery

From the Hubrecht Institute (L.W.v.L., R.P., C.L.M.), Utrecht; Heart Lung Center Utrecht (L.W.v.L., P.A.D.); and Department of Anatomy and Embryology (R.P., C.L.M.), Leiden University Medical Center, The Netherlands.

Correspondence to C. L. Mummery, Hubrecht Institute (Developmental Biology and Stem Cell Research), Uppsalalaan 8, 3584 CT Utrecht, The Netherlands. E-mail c.mummery{at}niob.knaw.nl

Cell transplantation may restore heart function in disease associated with loss or dysfunction of cardiomyocytes. Recently, Laflamme et al reported an improvement in cardiac function in immunodeficient rats 4 weeks after coronary artery ligation and injection of human embryonic stem cell–derived cardiomyocytes (hESC-CMs). We have recently carried out a comparable study transplanting hESC-CMs to the hearts of mice with myocardial infarction. Our findings were similar up to the 4-week time point, with significant improvements in cardiac function. However, our follow-up was longer, and, at 3 months, the difference between mice receiving cardiomyocytes and those receiving other cells was no longer significant. Hypothesizing that the improvement observed by Laflamme et al may have been more likely to be sustained long term because the grafts in their study appeared larger, we injected 3 times as many cells. Although this resulted in a significantly increased graft size, we again observed a functional improvement at 1 month but not at 3 months. Our results show that midterm data in these kinds of experiments must be interpreted with caution and longer-term follow-up is essential to draw conclusions on the efficacy of cardiac cell transplantation. Furthermore, our findings demonstrate the unlikely success of merely generating and injecting more cells of the same type to increase functional improvement.

Key Words: cell transplantation • MRI • myocardial infarction • stem cells

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