Scientific publications

Tomescot A, Leschik J, Bellamy V, Dubois G, Messas E, Bruneval P, Desnos M, Hagège AA, Amit M, Itskovitz J, Menasché P, Pucéat M.

 

INSERM, U 633; Assistance Publique-Hôpitaux de Paris, Ecole de Chirurgie, Paris, France.

 

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 alpha-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-beta 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.