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Insulin-Like Growth Factors Promote Vasculogenesis in Embryonic Stem Cells

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 en...

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Autores principales: Piecewicz, Stephanie M., Pandey, Ambarish, Roy, Bhaskar, Hua Xiang, Soh, Zetter, Bruce R., Sengupta, Shiladitya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283730/
https://www.ncbi.nlm.nih.gov/pubmed/22363814
http://dx.doi.org/10.1371/journal.pone.0032191
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author Piecewicz, Stephanie M.
Pandey, Ambarish
Roy, Bhaskar
Hua Xiang, Soh
Zetter, Bruce R.
Sengupta, Shiladitya
author_facet Piecewicz, Stephanie M.
Pandey, Ambarish
Roy, Bhaskar
Hua Xiang, Soh
Zetter, Bruce R.
Sengupta, Shiladitya
author_sort Piecewicz, Stephanie M.
collection PubMed
description 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.
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spelling pubmed-32837302012-02-23 Insulin-Like Growth Factors Promote Vasculogenesis in Embryonic Stem Cells Piecewicz, Stephanie M. Pandey, Ambarish Roy, Bhaskar Hua Xiang, Soh Zetter, Bruce R. Sengupta, Shiladitya PLoS One Research Article 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. Public Library of Science 2012-02-21 /pmc/articles/PMC3283730/ /pubmed/22363814 http://dx.doi.org/10.1371/journal.pone.0032191 Text en Piecewicz et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Piecewicz, Stephanie M.
Pandey, Ambarish
Roy, Bhaskar
Hua Xiang, Soh
Zetter, Bruce R.
Sengupta, Shiladitya
Insulin-Like Growth Factors Promote Vasculogenesis in Embryonic Stem Cells
title Insulin-Like Growth Factors Promote Vasculogenesis in Embryonic Stem Cells
title_full Insulin-Like Growth Factors Promote Vasculogenesis in Embryonic Stem Cells
title_fullStr Insulin-Like Growth Factors Promote Vasculogenesis in Embryonic Stem Cells
title_full_unstemmed Insulin-Like Growth Factors Promote Vasculogenesis in Embryonic Stem Cells
title_short Insulin-Like Growth Factors Promote Vasculogenesis in Embryonic Stem Cells
title_sort insulin-like growth factors promote vasculogenesis in embryonic stem cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283730/
https://www.ncbi.nlm.nih.gov/pubmed/22363814
http://dx.doi.org/10.1371/journal.pone.0032191
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