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EMBRYONIC STEM CELLS |
1 INSERM, U 633; Assistance Publique-Hôpitaux de Paris, Ecole de Chirurgie, Paris, France
2 INSERM UMR 861, I-stem, AFM Evry, France
3 INSERM U 633, Paris, France
4 Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Cardiology; University Paris-Descartes, Faculty of Medicine; INSERM U 633, Paris, France.
5 Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Pathology; University Paris-Descartes, Faculty of Medicine; INSERM U 430, Paris, France.
6 Technion Institute, Haifa, Israel
7 Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Cardiovascular Surgery; INSERM, U 633, Laboratoire de Recherches Biochirurgicales; University Paris-Descartes, Faculty of Medicine, Paris, France.
* To whom correspondence should be addressed. E-mail: mpuceat{at}istem.genethon.fr.
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Abstract |
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Human embryonic stem (HES) cells can give rise to cardiomyocytes in vitro. However whether undifferentiated HES cells also feature a myocardial regenerative capacity after in vivo engraftment has not been established yet.
We compared two HES cell lines (HUES-1 & I6) that were specified towards a cardiac lineage by exposure to bone morphogenetic protein (BMP2) and SU5402, a FGF receptor inhibitor. Real time PCR revealed that the cardiogenic inductive factor turned on expression of mesodermal and cardiac genes (Tbx6, Isl1, FoxH1, Nkx2.5, Mef2c, and 
-actin).
Thirty immunosuppressed rats underwent coronary artery ligation and, 2 weeks later, were randomized and received in-scar injections of either culture medium (controls) or BMP2 (±SU5402)-treated HES cells. After 2 months, human cells were detected by anti-human lamin immunostaining and their cardiomyocytic differentiation was evidenced by their expression of cardiac markers by RT-PCR and immunofluorescence using an anti-
myosin antibody. No teratoma was observed in hearts or any other organ of the body.
The ability of cardiac-specified HES cells to differentiate along the cardiomyogenic pathway following transplantation into infarcted myocardium raises the hope that these cells might become effective candidates for myocardial regeneration.
Key Words. Human embryonic stem cells, Cell transplantation, In vivo, cardiology
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