Mesenchymal Stem Cells Support Migration, Extracellular Matrix Invasion, Proliferation, and Survival of Endothelial Cells In Vitro
Article first published online: 29 MAR 2007
Copyright © 2007 AlphaMed Press
Volume 25, Issue 7, pages 1761–1768, July 2007
How to Cite
Potapova, I. A., Gaudette, G. R., Brink, P. R., Robinson, R. B., Rosen, M. R., Cohen, I. S. and Doronin, S. V. (2007), Mesenchymal Stem Cells Support Migration, Extracellular Matrix Invasion, Proliferation, and Survival of Endothelial Cells In Vitro. STEM CELLS, 25: 1761–1768. doi: 10.1634/stemcells.2007-0022
- Issue published online: 2 JAN 2009
- Article first published online: 29 MAR 2007
- Manuscript Accepted: 22 MAR 2007
- Manuscript Received: 11 JAN 2007
- Mesenchymal stem cells;
- Endothelial cells;
- Cell culture;
- Angiogenic cytokines
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.