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Insulin-like growth factor promotes cardiac lineage induction in vitro by selective expansion of early mesoderm.

Authors :
Engels MC
Rajarajan K
Feistritzer R
Sharma A
Nielsen UB
Schalij MJ
de Vries AA
Pijnappels DA
Wu SM
Source :
Stem cells (Dayton, Ohio) [Stem Cells] 2014 Jun; Vol. 32 (6), pp. 1493-502.
Publication Year :
2014

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.<br /> (© 2014 AlphaMed Press.)

Details

Language :
English
ISSN :
1549-4918
Volume :
32
Issue :
6
Database :
MEDLINE
Journal :
Stem cells (Dayton, Ohio)
Publication Type :
Academic Journal
Accession number :
24496962
Full Text :
https://doi.org/10.1002/stem.1660