Insulin-like growth factor promotes cardiac lineage induction in vitro by selective expansion of early mesoderm.
Stem Cells
; 32(6): 1493-502, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24496962
ABSTRACT
A thorough understanding of the developmental signals that direct pluripotent stem cells (PSCs) toward a cardiac fate is essential for translational applications in disease modeling and therapy. We screened a panel of 44 cytokines/signaling molecules for their ability to enhance Nkx2.5(+) cardiac progenitor cell (CPC) formation during in vitro embryonic stem cell (ESC) differentiation. Treatment of murine ESCs with insulin or insulin-like growth factors (IGF1/2) during early differentiation increased mesodermal cell proliferation and, consequently, CPC formation. Furthermore, we show that downstream mediators of IGF signaling (e.g., phospho-Akt and mTOR) are required for this effect. These data support a novel role for IGF family ligands to expand the developing mesoderm and promote cardiac differentiation. Insulin or IGF treatment could provide an effective strategy to increase the PSC-based generation of CPCs and cardiomyocytes for applications in regenerative medicine.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Insulin-Like I
/
Fator de Crescimento Insulin-Like II
/
Linhagem da Célula
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Mesoderma
/
Miocárdio
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Stem Cells
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Holanda