title: Differentiation in vivo of cardiac committed human embryonic stem cells in postmyocardial infarcted rats.
abstract: 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.
authors.affiliation: 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.
authors.forename: André
authors.initials: A
authors.lastname: Tomescot
authors.forename: Julia
authors.initials: J
authors.lastname: Leschik
authors.forename: Valérie
authors.initials: V
authors.lastname: Bellamy
authors.forename: Gilbert
authors.initials: G
authors.lastname: Dubois
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Messas
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: Michel
authors.initials: M
authors.lastname: Desnos
authors.forename: Albert A
authors.initials: AA
authors.lastname: Hagège
authors.forename: Michal
authors.initials: M
authors.lastname: Amit
authors.forename: Joseph
authors.initials: J
authors.lastname: Itskovitz
authors.forename: Philippe
authors.initials: P
authors.lastname: Menasché
authors.forename: Michel
authors.initials: M
authors.lastname: Pucéat
mesh_terms: 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