CD45+ Cells Present Within Mesenchymal Stem Cell Populations Affect Network Formation of Blood-Derived Endothelial Outgrowth Cells.
Abstract
Mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) represent promising
cell sources for angiogenic therapies. There are, however, conflicting reports regarding
the ability of MSCs to support network formation of endothelial cells. The goal of
this study was to assess the ability of human bone marrow-derived MSCs to support
network formation of endothelial outgrowth cells (EOCs) derived from umbilical cord
blood EPCs. We hypothesized that upon in vitro coculture, MSCs and EOCs promote a
microenvironment conducive for EOC network formation without the addition of angiogenic
growth supplements. EOC networks formed by coculture with MSCs underwent regression
and cell loss by day 10 with a near 4-fold and 2-fold reduction in branch points and
mean segment length, respectively, in comparison with networks formed by coculture
vascular smooth muscle cell (SMC) cocultures. EOC network regression in MSC cocultures
was not caused by lack of vascular endothelial growth factor (VEGF)-A or changes in
TGF-β1 or Ang-2 supernatant concentrations in comparison with SMC cocultures. Removal
of CD45+ cells from MSCs improved EOC network formation through a 2-fold increase
in total segment length and number of branch points in comparison to unsorted MSCs
by day 6. These improvements, however, were not sustained by day 10. CD45 expression
in MSC cocultures correlated with EOC network regression with a 5-fold increase between
day 6 and day 10 of culture. The addition of supplemental growth factors VEGF, fibroblastic
growth factor-2, EGF, hydrocortisone, insulin growth factor-1, ascorbic acid, and
heparin to MSC cocultures promoted stable EOC network formation over 2 weeks in vitro,
without affecting CD45 expression, as evidenced by a lack of significant differences
in total segment length (p=0.96). These findings demonstrate the ability of MSCs to
support EOC network formation correlates with removal of CD45+ cells and improves
upon the addition of soluble growth factors.
Type
Journal articleSubject
angiogenesisendothelial progenitor cells
mesenchymal stem cells
microvessel tissue engineering
umbilical cord blood
vasculogenesis
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https://hdl.handle.net/10161/10662Published Version (Please cite this version)
10.1089/biores.2014.0029Publication Info
Peters, Erica B; Christoforou, Nicolas; Moore, Erika; West, Jennifer L; & Truskey,
George A (2015). CD45+ Cells Present Within Mesenchymal Stem Cell Populations Affect Network Formation
of Blood-Derived Endothelial Outgrowth Cells. Biores Open Access, 4(1). pp. 75-88. 10.1089/biores.2014.0029. Retrieved from https://hdl.handle.net/10161/10662.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
George A. Truskey
R. Eugene and Susie E. Goodson Distinguished Professor of Biomedical Engineering
My research interests focus upon the effect of physical forces on the function of
vascular cells and skeletal muscle, cell adhesion, and the design of engineered tissues.
Current research projects examine the effect of endothelial cell senescence upon
permeability to macromolecules and the response to fluid shear stress, the development
of microphysiological blood vessels and muscles for evaluation of drug toxicity and
the design of engineered endothelialized blood vessels and skelet
Jennifer L West
Adjunct Professor of Biomedical Engineering
Jennifer West’s research in biomaterials and tissue engineering involves the synthesis,
development, and application of novel, biofunctional materials, and the use of biomaterials
and engineering approaches to study biological problems. Current projects include
the design of ECM-mimetic hydrogel materials, novel microfabrication strategies for
biomimetic patterning, and nanoparticle theranostics.
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