Insulin-Like Growth Factors Promote Vasculogenesis in Embryonic Stem Cells
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Piecewicz-2012-Insulin-like growth.pdf
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Author(s)
Piecewicz, Stephanie M.
Pandey, Ambarish
Roy, Bhaskar
Xiang, Soh Hua
Zetter, Bruce R.
Sengupta, Shiladitya
Date Issued
February 2012
Journal
PLoS ONE
Publisher
Public Library of Science
Citation
Piecewicz, Stephanie M. et al. “Insulin-Like Growth Factors Promote Vasculogenesis in Embryonic Stem Cells.” Ed. Gian Paolo Fadini. PLoS ONE 7.2 (2012): e32191.
Version
Final published version
Abstract
The ability of embryonic stem cells to differentiate into endothelium and form functional blood vessels has been well established and can potentially be harnessed for therapeutic angiogenesis. However, after almost two decades of investigation in this field, limited knowledge exists for directing endothelial differentiation. A better understanding of the cellular mechanisms regulating vasculogenesis is required for the development of embryonic stem cell-based models and therapies. In this study, we elucidated the mechanistic role of insulin-like growth factors (IGF1 and 2) and IGF receptors (IGFR1 and 2) in endothelial differentiation using an embryonic stem cell embryoid body model. Both IGF1 or IGF2 predisposed embryonic stem to differentiate towards a mesodermal lineage, the endothelial precursor germ layer, as well as increased the generation of significantly more endothelial cells at later stages. Inhibition of IGFR1 signaling using neutralizing antibody or a pharmacological inhibitor, picropodophyllin, significantly reduced IGF-induced mesoderm and endothelial precursor cell formation. We confirmed that IGF-IGFR1 signaling stabilizes HIF1α and leads to up-regulation of VEGF during vasculogenesis in embryoid bodies. Understanding the mechanisms that are critical for vasculogenesis in various models will bring us one step closer to enabling cell based therapies for neovascularization.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
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DOI of Published Version
https://doi.org/10.1371/journal.pone.0032191
