Mesenchymal Stem Cells Regulate Angiogenesis According to Their Mechanical Environment
Version of Record online: 11 JAN 2007
Copyright © 2007 AlphaMed Press
Volume 25, Issue 4, pages 903–910, April 2007
How to Cite
Kasper, G., Dankert, N., Tuischer, J., Hoeft, M., Gaber, T., Glaeser, J. D., Zander, D., Tschirschmann, M., Thompson, M., Matziolis, G. and Duda, G. N. (2007), Mesenchymal Stem Cells Regulate Angiogenesis According to Their Mechanical Environment. STEM CELLS, 25: 903–910. doi: 10.1634/stemcells.2006-0432
- Issue online: 2 JAN 2009
- Version of Record online: 11 JAN 2007
- Manuscript Accepted: 28 DEC 2006
- Manuscript Received: 14 JUL 2006
- Endothelial cells;
- Mesenchymal stem cells;
- Mechanical loading;
In fracture and bone defect healing, MSCs largely drive tissue regeneration. MSCs have been shown to promote angiogenesis both in vivo and in vitro. Angiogenesis is a prerequisite to large tissue reconstitution. The present study investigated how mechanical loading of MSCs influences their proangiogenic capacity. The results show a significant enhancement of angiogenesis by conditioned media from mechanically stimulated compared with unstimulated MSCs in two-dimensional tube formation and three-dimensional spheroid sprouting assays. In particular, proliferation but not migration or adhesion of endothelial cells was elevated. Promotion of angiogenesis was dependent upon fibroblast growth factor receptor 1 (FGFR1) signaling. Moreover, stimulation of tube formation was inhibited by vascular endothelial growth factor receptor (VEGFR) tyrosine kinase blocking. Screening for the expression levels of different soluble regulators of angiogenesis revealed an enrichment of matrix metalloprotease 2, transforming growth factor β1, and basic fibroblast growth factor but not of vascular endothelial growth factor in response to mechanical stimulation. In conclusion, mechanical loading of MSCs seems to result in a paracrine stimulation of angiogenesis, most likely by the regulation of a network of several angiogenic molecules. The underlying mechanism appears to be dependent on the FGFR and VEGFR signaling cascades and might be mediated by an additional cross-talk with other pathways.
Disclosure of potential conflicts of interest is found at the end of this article.