Differentiation in vivo of cardiac committed human embryonic stem cells in postmyocardial infarcted rats.
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 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 reverse transcription-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.
Tomescot
André
A
Institut National de la Santé et de la Recherche Médicale/Evry University Unité Mixte de Recherche 861, I-Stem, Association Française contre les Myopathies, 5, rue Desbrières, Evry 91030, France.
Leschik
Julia
J
Bellamy
Valérie
V
Dubois
Gilbert
G
Messas
Emmanuel
E
Bruneval
Patrick
P
Desnos
Michel
M
Hagège
Albert A
AA
Amit
Michal
M
Itskovitz
Joseph
J
Menasché
Philippe
P
Pucéat
Michel
M
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000637:transplantation*; D005260:Female; D006321:Heart / Q000502:physiology; D006801:Humans; D009203:Myocardial Infarction / Q000628:therapy*; D009206:Myocardium / Q000166:cytology*; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D014183:Transplantation, Heterologous