Sca-1+ progenitors derived from embryonic stem cells differentiate into endothelial cells capable of vascular repair after arterial injury.
BACKGROUND: Embryonic stem cells possess the ability to differentiate into endothelium. The ability to produce large volumes of endothelium from embryonic stem cells could provide a potential therapeutic modality for vascular injury. We describe an approach that selects endothelial cells using magn...
| Main Authors: | , , , , , , , |
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| פורמט: | Journal article |
| שפה: | English |
| יצא לאור: |
2006
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| _version_ | 1826271444591443968 |
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| author | Xiao, Q Zeng, L Zhang, Z Margariti, A Ali, Z Channon, K Xu, Q Hu, Y |
| author_facet | Xiao, Q Zeng, L Zhang, Z Margariti, A Ali, Z Channon, K Xu, Q Hu, Y |
| author_sort | Xiao, Q |
| collection | OXFORD |
| description | BACKGROUND: Embryonic stem cells possess the ability to differentiate into endothelium. The ability to produce large volumes of endothelium from embryonic stem cells could provide a potential therapeutic modality for vascular injury. We describe an approach that selects endothelial cells using magnetic beads that may be used therapeutically to treat arterial injury. METHODS AND RESULTS: Large numbers of endothelial cells (ECs) with high purity were produced using Sca-1+ cells isolated with magnetic beads from predifferentiated embryonic stem cells (ESCs) cultured in alpha-MEM containing 10 ng/mL VEGF165 for a minimum of 21 days (esEC). The transcription regulator histone deacetylase (HDAC3) was essential for VEGF-induced EC differentiation. Immunofluorescence or fluorescence-activated cell sorter (FACS) analysis revealed that esECs expressed a full range of EC lineage-specific markers including CD31, CD106, CD144, Flk-1, Flt-1, and von Willebrand factor (vWF). FACS analysis confirmed that 99% of esECs were CD31-positive and 75% vWF-positive. Furthermore, almost all cells were positive for DiI-acLDL uptake. When matrigel containing esECs was subcutaneously implanted into mice, various vessel-like structures were observed indicating their endothelial cell like phenotype. In keeping with this, when esECs infected with adenovirus-LacZ were injected into denuded femoral arteries of mice, they were found to form a neo-endothelium that covered the injured areas (86%+/-13.6%), which resulted in a 73% decrease in neointimal area 2 weeks after injury. CONCLUSIONS: We conclude that Sca-1+ cells can differentiate into functional ECs via activation of HDAC3, accelerating re-endothelialization of injured arteries and reducing neointima formation. |
| first_indexed | 2024-03-06T21:56:46Z |
| format | Journal article |
| id | oxford-uuid:4d2d44cf-f8e0-4c7d-a9ef-0e5251c90307 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:56:46Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:4d2d44cf-f8e0-4c7d-a9ef-0e5251c903072022-03-26T15:53:57ZSca-1+ progenitors derived from embryonic stem cells differentiate into endothelial cells capable of vascular repair after arterial injury.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4d2d44cf-f8e0-4c7d-a9ef-0e5251c90307EnglishSymplectic Elements at Oxford2006Xiao, QZeng, LZhang, ZMargariti, AAli, ZChannon, KXu, QHu, Y BACKGROUND: Embryonic stem cells possess the ability to differentiate into endothelium. The ability to produce large volumes of endothelium from embryonic stem cells could provide a potential therapeutic modality for vascular injury. We describe an approach that selects endothelial cells using magnetic beads that may be used therapeutically to treat arterial injury. METHODS AND RESULTS: Large numbers of endothelial cells (ECs) with high purity were produced using Sca-1+ cells isolated with magnetic beads from predifferentiated embryonic stem cells (ESCs) cultured in alpha-MEM containing 10 ng/mL VEGF165 for a minimum of 21 days (esEC). The transcription regulator histone deacetylase (HDAC3) was essential for VEGF-induced EC differentiation. Immunofluorescence or fluorescence-activated cell sorter (FACS) analysis revealed that esECs expressed a full range of EC lineage-specific markers including CD31, CD106, CD144, Flk-1, Flt-1, and von Willebrand factor (vWF). FACS analysis confirmed that 99% of esECs were CD31-positive and 75% vWF-positive. Furthermore, almost all cells were positive for DiI-acLDL uptake. When matrigel containing esECs was subcutaneously implanted into mice, various vessel-like structures were observed indicating their endothelial cell like phenotype. In keeping with this, when esECs infected with adenovirus-LacZ were injected into denuded femoral arteries of mice, they were found to form a neo-endothelium that covered the injured areas (86%+/-13.6%), which resulted in a 73% decrease in neointimal area 2 weeks after injury. CONCLUSIONS: We conclude that Sca-1+ cells can differentiate into functional ECs via activation of HDAC3, accelerating re-endothelialization of injured arteries and reducing neointima formation. |
| spellingShingle | Xiao, Q Zeng, L Zhang, Z Margariti, A Ali, Z Channon, K Xu, Q Hu, Y Sca-1+ progenitors derived from embryonic stem cells differentiate into endothelial cells capable of vascular repair after arterial injury. |
| title | Sca-1+ progenitors derived from embryonic stem cells differentiate into endothelial cells capable of vascular repair after arterial injury. |
| title_full | Sca-1+ progenitors derived from embryonic stem cells differentiate into endothelial cells capable of vascular repair after arterial injury. |
| title_fullStr | Sca-1+ progenitors derived from embryonic stem cells differentiate into endothelial cells capable of vascular repair after arterial injury. |
| title_full_unstemmed | Sca-1+ progenitors derived from embryonic stem cells differentiate into endothelial cells capable of vascular repair after arterial injury. |
| title_short | Sca-1+ progenitors derived from embryonic stem cells differentiate into endothelial cells capable of vascular repair after arterial injury. |
| title_sort | sca 1 progenitors derived from embryonic stem cells differentiate into endothelial cells capable of vascular repair after arterial injury |
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