Efficient cardiomyogenic differentiation of embryonic stem cell by fibroblast growth factor 2 and bone morphogenetic protein 2.
BACKGROUND
Despite the pluripotency of embryonic stem (ES) cells, the specific control of their cardiomyogenic differentiation remains difficult. The aim of the present study was to investigate whether growth factors may efficiently enhance the in vitro cardiac differentiation of ES cells.


RESULTS
Recombinant growth factors at various concentrations or their inhibitors were added according to various schedules during the cardiomyogenic differentiation of ES cells. Cardiomyogenic differentiation was assessed by mRNA and protein expressions of several cardiomyocyte-specific genes. Basic fibroblast growth factor-2 (FGF-2) and/or bone morphogenetic protein-2 (BMP-2) efficiently enhanced the cardiomyogenic differentiation, but only when they were added at the optimal concentration (1.0 ng/ml in FGF-2 and 0.2 ng/ml in BMP-2; relatively lower than expected in both cases) for the first 3 days. Inhibition of FGF-2 and/or BMP-2 drastically suppressed the cardiomyogenic differentiation.


CONCLUSIONS
FGF-2 and BMP-2 play a crucial role in early cardiomyogenesis. The achievement of efficient cardiac differentiation using both growth factors may facilitate ES cell-derived cell therapy for heart diseases as well as contribute to developmental studies of the heart.
Kawai
Takao
T
Cardiology, Respiratory and Nephrology, Regeneration and Advanced Medical Science, Graduate School of Medicine, Gifu University, Gifu, Japan.
Takahashi
Tomoyuki
T
Esaki
Masayasu
M
Ushikoshi
Hiroaki
H
Nagano
Satoshi
S
Fujiwara
Hisayoshi
H
Kosai
Ken-Ichiro
K
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D017931:DNA Primers; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D051379:Mice; D009206:Myocardium / Q000166:cytology; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000235:genetics*
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D012313:RNA