Differentiation In Vivo of Cardiac Committed Human Embryonic Stem Cells in Postmyocardial Infarcted Rats
Article first published online: 31 MAY 2007
Copyright © 2007 AlphaMed Press
Volume 25, Issue 9, pages 2200–2205, September 2007
How to Cite
Tomescot, A., Leschik, J., Bellamy, V., Dubois, G., Messas, E., Bruneval, P., Desnos, M., Hagège, A. A., Amit, M., Itskovitz, J., Menasché, P. and Pucéat, M. (2007), Differentiation In Vivo of Cardiac Committed Human Embryonic Stem Cells in Postmyocardial Infarcted Rats. STEM CELLS, 25: 2200–2205. doi: 10.1634/stemcells.2007-0133
- Issue published online: 2 JAN 2009
- Article first published online: 31 MAY 2007
- Manuscript Accepted: 23 MAY 2007
- Manuscript Received: 22 FEB 2007
- Human embryonic stem cells;
- Cell transplantation;
- In vivo;
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 and I6) that were specified toward a cardiac lineage by exposure to bone morphogenetic protein-2 (BMP2) and SU5402, a fibroblast growth factor receptor inhibitor. Real-time polymerase chain reaction (PCR) revealed that the cardiogenic inductive factor turned on expression of mesodermal and cardiac genes (Tbx6, Isl1, FoxH1, Nkx2.5, Mef2c, and α-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 reverse transcription-PCR and immunofluorescence using an anti-β 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.
Disclosure of potential conflicts of interest is found at the end of this article.