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Front. Med. | doi: 10.3389/fmed.2018.00356

HYPOXIA IMPAIRS INITIAL OUTGROWTH OF ENDOTHELIAL COLONY FORMING CELLS AND REDUCES THEIR PROLIFERATIVE AND SPROUTING POTENTIAL

 Victor W. Van Hinsbergh1, 2*, Dimitar Tasev2, Laura Dekker3, Michiel van Wijhe2, Henk J. Broxterman3 and  Pieter Koolwijk2
  • 1VU University Medical Center, Netherlands
  • 2Department of Physiology, Medical Center, VU University Amsterdam, Netherlands
  • 3Department of Medical Oncology, Medical Center, VU University Amsterdam, Netherlands

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 at 20% and 1% O2 cell culture conditions. Clonal outgrowth was followed during a 30 days 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 (18±2% reduction); proliferation of PB-ECFCs was reduced to a similar extent. Early passages of subcultured CB- and PB-ECFCs contained only viable cells and few if any senescent cells, but the clonal ability of subcultured PB-ECFCs was reduced by 30% for PB-ECFCs. 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.

Keywords: ECFCs, , hypoxia, Colony growth, Angiogenesis, tissue repair, proliferation

Received: 18 Jun 2018; Accepted: 06 Dec 2018.

Edited by:

Reinhold J. Medina, Queen's University Belfast, United Kingdom

Reviewed by:

Kazuhide Hayakawa, Department of Radiology, Massachusetts General Hospital, United States
Chad L. Barber, California Lutheran University, United States  

Copyright: © 2018 Van Hinsbergh, Tasev, Dekker, van Wijhe, Broxterman and Koolwijk. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Victor W. Van Hinsbergh, VU University Medical Center, Amsterdam, Netherlands, v.vanhinsbergh@vumc.nl