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TISSUE-SPECIFIC STEM CELLS

Mesenchymal Stem Cells Support Migration, Extracellular Matrix Invasion, Proliferation, and Survival of Endothelial Cells In Vitro

^aDepartment of Physiology and Biophysics, Institute of Molecular Cardiology, State University of New York at Stony Brook, Stony Brook, New York, USA;
^bDepartment of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts, USA;
^cCenter for Molecular Therapeutics and
Departments of ^dPharmacology and
^ePediatrics, Columbia University, New York, New York, USA

Key Words. Mesenchymal stem cells • Endothelial cells • Cell culture • Angiogenic cytokines

Correspondence: Sergey Doronin, Ph.D., Department of Physiology and Biophysics, BST-6, Room 124, University of New York at Stony Brook, Stony Brook, New York 11794, USA. Telephone: 631-444-7373; Fax: 631-444-3432; e-mail: sdoronin{at}notes.cc.sunysb.edu

Received January 11, 2007; accepted for publication March 22, 2007.
First published online in STEM CELLS EXPRESS   March 29, 2007.



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.