Mesenchymal stem cells support migration, extracellular matrix invasion, proliferation, and survival of endothelial cells in vitro.
We investigated effects of the paracrine factors secreted by human mesenchymal stem cells (hMSCs) on endothelial cell migration, extracellular matrix invasion, proliferation, and survival in vitro. Human mesenchymal stem cells were cultured as a monolayer or as three-dimensional aggregates in hanging drops (hMSC spheroids). We performed analysis of paracrine factors in medium conditioned by a monolayer of hMSCs and hMSC spheroids. Concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor, angiogenin, procathepsin B, interleukin (IL)-11, and bone morphogenic protein 2 were increased 5-20 times in medium conditioned by hMSC spheroids, whereas concentrations of IL-6, IL-8, and monocyte hemoattractant protein-1 were not increased. Concentrations of VEGF and angiogenin in medium conditioned by hMSC spheroids showed a weak dependence on the presence of serum, which allows serum-free conditioned medium with elevated concentrations of angiogenic cytokines to be obtained. Medium conditioned by hMSC spheroids was more effective in stimulation of umbilical vein endothelial cell proliferation, migration, and basement membrane invasion than medium conditioned by a monolayer of hMSCs. This medium also promotes endothelial cell survival in vitro. We suggest that culturing of hMSCs as three-dimensional cellular aggregates provides a method to concentrate proangiogenic factors secreted by hMSCs and allows for reduction of serum concentration in conditioned medium. Our data support the hypothesis that hMSCs serve as trophic mediators for endothelial cells. Disclosure of potential conflicts of interest is found at the end of this article.
Potapova
Irina A
IA
Department of Physiology and Biophysics, University of New York at Stony Brook, Stony Brook, New York 11794, USA.
Gaudette
Glenn R
GR
Brink
Peter R
PR
Robinson
Richard B
RB
Rosen
Michael R
MR
Cohen
Ira S
IS
Doronin
Sergey V
SV
D001485:Basement Membrane / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D042783:Endothelial Cells / Q000166:cytology*; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000166:cytology; D014471:Umbilical Veins / Q000166:cytology
D017077:Culture Media, Conditioned; D016207:Cytokines; D004247:DNA; D001973:Bromodeoxyuridine