title: The impact of proliferative potential of umbilical cord-derived endothelial progenitor cells and hypoxia on vascular tubule formation in vitro.
abstract: Revascularization of the damaged tissue is pivotal to tissue repair. Here, by bringing together two in vitro model systems, we have been able to examine (1) the ability of human umbilical vein endothelial cells (HUVEC) containing a complete hierarchy of endothelial progenitors derived from the human umbilical cord to generate vascular tubules within a human stromal niche in vitro and (2) the effects of exposure to low oxygen tensions on endothelial progenitor cell proliferation and tubule formation in vitro. Our results demonstrate that high proliferative potential endothelial colony forming cells (HPP-ECFC) from cultured HUVEC preferentially contribute to vascular tubule formation in vitro and that these progenitor cells are concentrated in the CD34(lo/-) fraction. HUVEC were initially resistant when exposed to hypoxia (1.5% O(2)) for short periods (1-2 days), but sustained chronic hypoxia (4-14 days) inhibited their ability to proliferate. This was reflected by a loss in their ability to form tubules in cocultures of human dermal fibroblasts (hDFs). In contrast, an acute exposure to low oxygen tensions (1.5% O(2) for 24 h) followed by reoxygenation did not adversely affect the capacity of these cells to both proliferate and form vascular tubules in vitro.These studies therefore provide a model system to study the influences of the microenvironmental niche and modification of this niche on vascular tubule formation in vitro from HPP-ECFC.
authors.affiliation: Stem Cell Research Laboratory, NHS Blood and Transplant, Oxford, United Kingdom.
authors.forename: Youyi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Nita
authors.initials: N
authors.lastname: Fisher
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Newey
authors.forename: Jon
authors.initials: J
authors.lastname: Smythe
authors.forename: Louise
authors.initials: L
authors.lastname: Tatton
authors.forename: Grigorios
authors.initials: G
authors.lastname: Tsaknakis
authors.forename: Sinead P
authors.initials: SP
authors.lastname: Forde
authors.forename: Lee
authors.initials: L
authors.lastname: Carpenter
authors.forename: Thanassi
authors.initials: T
authors.lastname: Athanassopoulos
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Hale
authors.forename: David J P
authors.initials: DJ
authors.lastname: Ferguson
authors.forename: Michael P
authors.initials: MP
authors.lastname: Tyler
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Watt
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis; D002452:Cell Count; D015687:Cell Hypoxia; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D002999:Clone Cells; D018920:Coculture Techniques; D003114:Colony-Forming Units Assay; D020405:Dermis / Q000166:cytology; D042783:Endothelial Cells / Q000166:cytology* / Q000648:ultrastructure; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D009336:Necrosis; D018919:Neovascularization, Physiologic; D013234:Stem Cells / Q000166:cytology* / Q000648:ultrastructure; D014470:Umbilical Cord / Q000166:cytology*; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D018952:Antigens, CD34