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First published online March 29, 2007
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2007-0022v1
25/7/1761    most recent
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Submitted on January 11, 2007
Accepted on March 22, 2007

Tissue-Specific Stem Cells

Mesenchymal stem cells support migration, extracellular matrix invasion, proliferation and survival of endothelial cells in vitro

Irina A. Potapova 1, Glenn R. Gaudette 2, Peter R. Brink 1, Richard B. Robinson 3, Michael R. Rosen 3, Ira S. Cohen 1, Sergey V. Doronin 1*

1 Department of Physiology and Biophysics, Institute of Molecular Cardiology, State University of New York at Stony Brook, Stony Brook, New York
2 Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts
3 Center for Molecular Therapeutics & Departments of Pharmacology and Pediatrics, Columbia University, New York, New York

* To whom correspondence should be addressed. E-mail: sdoronin{at}notes.cc.sunysb.edu.


  Abstract

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 3D-agregates in hanging drops (hMSC spheroids). We performed analysis of paracrine factors in media conditioned by a monolayer hMSCs and hMSC spheroids. Concentrations of VEGF, basic FGF, angiogenin, pro-cathepsin B, IL-11 and BMP-2 were increased form 5 to 20 times in media conditioned by hMSC spheroids while concentrations of IL-6, IL-8 and MCP-1 were not increased. Concentrations of VEGF and angiogenin in media conditioned by hMSC spheroids showed a weak dependence on the presence of serum which allows obtaining serum free conditioned media with elevated concentrations of angiogenic cytokines. Media conditioned by hMSC spheroids was more effective in stimulation of umbilical vein endothelial cell proliferation, migration, and basement membrane invasion than media conditioned by a monolayer of hMSCs. This media also promotes endothelial cell survival in vitro. We suggest that culturing of hMSCs as three-dimensional cellular aggregates provides a method to concentrate pro-angiogenic factors secreted by hMSCs and allows for reduction of serum concentration in conditioned media. Our data support the hypothesis that hMSCs serve as trophic mediators for endothelial cells.

Key Words. mesenchymal stem cells, endothelial cells, cell culture, angiogenic cytokines




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[Abstract] [Full Text] [PDF]


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