Hypoxia Impairs Initial Outgrowth of Endothelial Colony Forming Cells and Reduces Their Proliferative and Sprouting Potential
Vascular homeostasis and regeneration in ischemic tissue relies on intrinsic competence of the tissue to rapidly recruit endothelial cells for vascularization. The mononuclear cell (MNC) fraction of blood contains circulating progenitors committed to endothelial lineage. These progenitors give rise...
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| Format: | Article |
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Frontiers Media S.A.
2018-12-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmed.2018.00356/full |
| _version_ | 1819015692685410304 |
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| author | Dimitar Tasev Laura Dekker-Vroling Michiel van Wijhe Henk J. Broxterman Pieter Koolwijk Victor W. M. van Hinsbergh |
| author_facet | Dimitar Tasev Laura Dekker-Vroling Michiel van Wijhe Henk J. Broxterman Pieter Koolwijk Victor W. M. van Hinsbergh |
| author_sort | Dimitar Tasev |
| collection | DOAJ |
| description | Vascular homeostasis and regeneration in ischemic tissue relies on intrinsic competence of the tissue to rapidly recruit endothelial cells for vascularization. The mononuclear cell (MNC) fraction of blood contains circulating progenitors committed to endothelial lineage. These progenitors give rise to endothelial colony-forming cells (ECFCs) that actively participate in neovascularization of ischemic tissue. To evaluate if the initial clonal outgrowth of ECFCs from cord (CB) and peripheral blood (PB) was stimulated by hypoxic conditions, MNCs obtained from CB and PB were subjected to 20 and 1% O2 cell culture conditions. Clonal outgrowth was followed during a 30 day incubation period. Hypoxia impaired the initial outgrowth of ECFC colonies from CB and also reduced their number that were developing from PB MNCs. Three days of oxygenation (20% O2) prior to hypoxia could overcome the initial CB-ECFC outgrowth. Once proliferating and subcultured the CB-ECFCs growth was only modestly affected by hypoxia; proliferation of PB-ECFCs was reduced to a similar extent (18–30% reduction). Early passages of subcultured CB- and PB-ECFCs contained only viable cells and few if any senescent cells. Tube formation by subcultured PB-ECFCs was also markedly inhibited by continuous exposure to 1% O2. Gene expression profiles point to regulation of the cell cycle and metabolism as major altered gene clusters. Finally we discuss our counterintuitive observations in the context of the important role that hypoxia has in promoting neovascularization. |
| first_indexed | 2024-12-21T02:35:47Z |
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| id | doaj.art-e8bb01119da5463d81c6c8bb4b67cac9 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-21T02:35:47Z |
| publishDate | 2018-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-e8bb01119da5463d81c6c8bb4b67cac92022-12-21T19:18:48ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2018-12-01510.3389/fmed.2018.00356408853Hypoxia Impairs Initial Outgrowth of Endothelial Colony Forming Cells and Reduces Their Proliferative and Sprouting PotentialDimitar Tasev0Laura Dekker-Vroling1Michiel van Wijhe2Henk J. Broxterman3Pieter Koolwijk4Victor W. M. van Hinsbergh5Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, Amsterdam, NetherlandsDepartment of Medical Oncology, Amsterdam University Medical Centers, Amsterdam, NetherlandsDepartment of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, Amsterdam, NetherlandsDepartment of Medical Oncology, Amsterdam University Medical Centers, Amsterdam, NetherlandsDepartment of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, Amsterdam, NetherlandsDepartment of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, Amsterdam, NetherlandsVascular homeostasis and regeneration in ischemic tissue relies on intrinsic competence of the tissue to rapidly recruit endothelial cells for vascularization. The mononuclear cell (MNC) fraction of blood contains circulating progenitors committed to endothelial lineage. These progenitors give rise to endothelial colony-forming cells (ECFCs) that actively participate in neovascularization of ischemic tissue. To evaluate if the initial clonal outgrowth of ECFCs from cord (CB) and peripheral blood (PB) was stimulated by hypoxic conditions, MNCs obtained from CB and PB were subjected to 20 and 1% O2 cell culture conditions. Clonal outgrowth was followed during a 30 day incubation period. Hypoxia impaired the initial outgrowth of ECFC colonies from CB and also reduced their number that were developing from PB MNCs. Three days of oxygenation (20% O2) prior to hypoxia could overcome the initial CB-ECFC outgrowth. Once proliferating and subcultured the CB-ECFCs growth was only modestly affected by hypoxia; proliferation of PB-ECFCs was reduced to a similar extent (18–30% reduction). Early passages of subcultured CB- and PB-ECFCs contained only viable cells and few if any senescent cells. Tube formation by subcultured PB-ECFCs was also markedly inhibited by continuous exposure to 1% O2. Gene expression profiles point to regulation of the cell cycle and metabolism as major altered gene clusters. Finally we discuss our counterintuitive observations in the context of the important role that hypoxia has in promoting neovascularization.https://www.frontiersin.org/article/10.3389/fmed.2018.00356/fullECFCshypoxiacolony growthangiogenesistissue repairproliferation |
| spellingShingle | Dimitar Tasev Laura Dekker-Vroling Michiel van Wijhe Henk J. Broxterman Pieter Koolwijk Victor W. M. van Hinsbergh Hypoxia Impairs Initial Outgrowth of Endothelial Colony Forming Cells and Reduces Their Proliferative and Sprouting Potential Frontiers in Medicine ECFCs hypoxia colony growth angiogenesis tissue repair proliferation |
| title | Hypoxia Impairs Initial Outgrowth of Endothelial Colony Forming Cells and Reduces Their Proliferative and Sprouting Potential |
| title_full | Hypoxia Impairs Initial Outgrowth of Endothelial Colony Forming Cells and Reduces Their Proliferative and Sprouting Potential |
| title_fullStr | Hypoxia Impairs Initial Outgrowth of Endothelial Colony Forming Cells and Reduces Their Proliferative and Sprouting Potential |
| title_full_unstemmed | Hypoxia Impairs Initial Outgrowth of Endothelial Colony Forming Cells and Reduces Their Proliferative and Sprouting Potential |
| title_short | Hypoxia Impairs Initial Outgrowth of Endothelial Colony Forming Cells and Reduces Their Proliferative and Sprouting Potential |
| title_sort | hypoxia impairs initial outgrowth of endothelial colony forming cells and reduces their proliferative and sprouting potential |
| topic | ECFCs hypoxia colony growth angiogenesis tissue repair proliferation |
| url | https://www.frontiersin.org/article/10.3389/fmed.2018.00356/full |
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