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...
| Main Authors: | , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Public Library of Science
2012
|
| Online Access: | http://hdl.handle.net/1721.1/71785 |
| _version_ | 1826210448292184064 |
|---|---|
| author | Piecewicz, Stephanie M. Pandey, Ambarish Roy, Bhaskar Xiang, Soh Hua Zetter, Bruce R. Sengupta, Shiladitya |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Piecewicz, Stephanie M. Pandey, Ambarish Roy, Bhaskar Xiang, Soh Hua Zetter, Bruce R. Sengupta, Shiladitya |
| author_sort | Piecewicz, Stephanie M. |
| collection | MIT |
| 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. |
| first_indexed | 2024-09-23T14:49:44Z |
| format | Article |
| id | mit-1721.1/71785 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:49:44Z |
| publishDate | 2012 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/717852022-10-01T22:44:37Z Insulin-Like Growth Factors Promote Vasculogenesis in Embryonic Stem Cells Piecewicz, Stephanie M. Pandey, Ambarish Roy, Bhaskar Xiang, Soh Hua Zetter, Bruce R. Sengupta, Shiladitya Harvard University--MIT Division of Health Sciences and Technology Shiladitya, Sengupta Piecewicz, Stephanie M. Sengupta, Shiladitya 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. United States. Dept. of Defense. Hope Scholar Award (W81XWH-07-1-0482) American Heart Association. Scientist Development Grant 2012-07-24T17:30:46Z 2012-07-24T17:30:46Z 2012-02 2011-08 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/71785 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. en_US http://dx.doi.org/10.1371/journal.pone.0032191 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Piecewicz, Stephanie M. Pandey, Ambarish Roy, Bhaskar Xiang, Soh Hua 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 |
| url | http://hdl.handle.net/1721.1/71785 |
| work_keys_str_mv | AT piecewiczstephaniem insulinlikegrowthfactorspromotevasculogenesisinembryonicstemcells AT pandeyambarish insulinlikegrowthfactorspromotevasculogenesisinembryonicstemcells AT roybhaskar insulinlikegrowthfactorspromotevasculogenesisinembryonicstemcells AT xiangsohhua insulinlikegrowthfactorspromotevasculogenesisinembryonicstemcells AT zetterbrucer insulinlikegrowthfactorspromotevasculogenesisinembryonicstemcells AT senguptashiladitya insulinlikegrowthfactorspromotevasculogenesisinembryonicstemcells |