Disrupted Endothelial Cell Layer and Exposed Extracellular Matrix Proteins Promote Capture of Late Outgrowth Endothelial Progenitor Cells
Late outgrowth endothelial progenitor cells (LO-EPC) possess a high proliferative potential, differentiate into vascular endothelial cells (EC), and form networks, suggesting they play a role in vascular repair. However, due to their scarcity in the circulation there is a requirement for ex vivo exp...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2016/1406304 |
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| author | Jing Zhao Claudia-Gabriela Mitrofan Sarah L. Appleby Nicholas W. Morrell Andrew M. L. Lever |
| author_facet | Jing Zhao Claudia-Gabriela Mitrofan Sarah L. Appleby Nicholas W. Morrell Andrew M. L. Lever |
| author_sort | Jing Zhao |
| collection | DOAJ |
| description | Late outgrowth endothelial progenitor cells (LO-EPC) possess a high proliferative potential, differentiate into vascular endothelial cells (EC), and form networks, suggesting they play a role in vascular repair. However, due to their scarcity in the circulation there is a requirement for ex vivo expansion before they could provide a practical cell therapy and it is currently unclear if they would home and engraft to an injury site. Using an in vitro flow system we studied LO-EPC under simulated injury conditions including EC activation, ischaemia, disrupted EC integrity, and exposed basement membrane. Perfused LO-EPC adhered to discontinuous EC paracellularly at junctional regions between adjacent cells under shear stress 0.7 dyn/cm2. The interaction was not adhesion molecule-dependent and not enhanced by EC activation. LO-EPC expressed high levels of the VE-Cadherin which may explain these findings. Ischaemia reperfusion injury decreased the interaction with LO-EPC due to cell retraction. LO-EPC interacted with exposed extracellular matrix (ECM) proteins, fibronectin and vitronectin. The interaction was mediated by integrins α5β3, αvβ1, and αvβ3. This study has demonstrated that an injured local environment presents sufficient adhesive signals to capture flow perfused LO-EPC in vitro and that LO-EPC have properties consistent with their potential role in vascular repair. |
| format | Article |
| id | doaj-art-5a6dcf407dc04ec8aa53f279a514481b |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-5a6dcf407dc04ec8aa53f279a514481b2025-02-03T05:52:33ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/14063041406304Disrupted Endothelial Cell Layer and Exposed Extracellular Matrix Proteins Promote Capture of Late Outgrowth Endothelial Progenitor CellsJing Zhao0Claudia-Gabriela Mitrofan1Sarah L. Appleby2Nicholas W. Morrell3Andrew M. L. Lever4Department of Medicine, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, UKDepartment of Medicine, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, UKDepartment of Medicine, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, UKDepartment of Medicine, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, UKDepartment of Medicine, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, UKLate outgrowth endothelial progenitor cells (LO-EPC) possess a high proliferative potential, differentiate into vascular endothelial cells (EC), and form networks, suggesting they play a role in vascular repair. However, due to their scarcity in the circulation there is a requirement for ex vivo expansion before they could provide a practical cell therapy and it is currently unclear if they would home and engraft to an injury site. Using an in vitro flow system we studied LO-EPC under simulated injury conditions including EC activation, ischaemia, disrupted EC integrity, and exposed basement membrane. Perfused LO-EPC adhered to discontinuous EC paracellularly at junctional regions between adjacent cells under shear stress 0.7 dyn/cm2. The interaction was not adhesion molecule-dependent and not enhanced by EC activation. LO-EPC expressed high levels of the VE-Cadherin which may explain these findings. Ischaemia reperfusion injury decreased the interaction with LO-EPC due to cell retraction. LO-EPC interacted with exposed extracellular matrix (ECM) proteins, fibronectin and vitronectin. The interaction was mediated by integrins α5β3, αvβ1, and αvβ3. This study has demonstrated that an injured local environment presents sufficient adhesive signals to capture flow perfused LO-EPC in vitro and that LO-EPC have properties consistent with their potential role in vascular repair.http://dx.doi.org/10.1155/2016/1406304 |
| spellingShingle | Jing Zhao Claudia-Gabriela Mitrofan Sarah L. Appleby Nicholas W. Morrell Andrew M. L. Lever Disrupted Endothelial Cell Layer and Exposed Extracellular Matrix Proteins Promote Capture of Late Outgrowth Endothelial Progenitor Cells Stem Cells International |
| title | Disrupted Endothelial Cell Layer and Exposed Extracellular Matrix Proteins Promote Capture of Late Outgrowth Endothelial Progenitor Cells |
| title_full | Disrupted Endothelial Cell Layer and Exposed Extracellular Matrix Proteins Promote Capture of Late Outgrowth Endothelial Progenitor Cells |
| title_fullStr | Disrupted Endothelial Cell Layer and Exposed Extracellular Matrix Proteins Promote Capture of Late Outgrowth Endothelial Progenitor Cells |
| title_full_unstemmed | Disrupted Endothelial Cell Layer and Exposed Extracellular Matrix Proteins Promote Capture of Late Outgrowth Endothelial Progenitor Cells |
| title_short | Disrupted Endothelial Cell Layer and Exposed Extracellular Matrix Proteins Promote Capture of Late Outgrowth Endothelial Progenitor Cells |
| title_sort | disrupted endothelial cell layer and exposed extracellular matrix proteins promote capture of late outgrowth endothelial progenitor cells |
| url | http://dx.doi.org/10.1155/2016/1406304 |
| work_keys_str_mv | AT jingzhao disruptedendothelialcelllayerandexposedextracellularmatrixproteinspromotecaptureoflateoutgrowthendothelialprogenitorcells AT claudiagabrielamitrofan disruptedendothelialcelllayerandexposedextracellularmatrixproteinspromotecaptureoflateoutgrowthendothelialprogenitorcells AT sarahlappleby disruptedendothelialcelllayerandexposedextracellularmatrixproteinspromotecaptureoflateoutgrowthendothelialprogenitorcells AT nicholaswmorrell disruptedendothelialcelllayerandexposedextracellularmatrixproteinspromotecaptureoflateoutgrowthendothelialprogenitorcells AT andrewmllever disruptedendothelialcelllayerandexposedextracellularmatrixproteinspromotecaptureoflateoutgrowthendothelialprogenitorcells |