Regulation of Mesenchymal Stem Cell Activity by Endothelial Cells
- 1 March 2011
- journal article
- research article
- Published by Mary Ann Liebert Inc in Stem Cells and Development
- Vol. 20 (3), 391-403
- https://doi.org/10.1089/scd.2010.0168
Abstract
Emerging data suggest that mesenchymal stem cells (MSCs) are part of a periendothelial niche, suggesting the existence of heterotypic cell–cell crosstalk between endothelial cells and MSCs that regulate MSCs in their local microenvironment. We determined the effects of paracrine factors secreted by human umbilical vein endothelial cells (HUVECs) on MSC survival, proliferation, and differentiation by using an optimized, serum-free HUVEC-conditioned medium (CM). HUVEC-CM induced a significant increase in the size and number of colony-forming units–fibroblast (CFU-F) and CFU-osteoblast (CFU-O) and stimulated the proliferation of MSCs as determined by 5-bromo-2′-deoxyuridine incorporation, compared with non-CM. We also demonstrated that CM significantly enhanced the osteogenic differentiation of MSCs as shown by alkaline phosphatase enzyme histochemistry and von Kossa staining of mineralized nodules as well as by quantitative reverse transcriptase–polymerase chain reaction analysis of osteogenic markers. In contrast, there was no effect on the adipogenic differentiation of MSCs. Bioinformatic integration of HUVEC and MSC gene expression datasets identified several candidate signaling pathways responsible for mediating these effects, including fibroblast growth factor, Wnt, bone morphogenetic protein, and Notch. These data suggest strongly that endothelial cells secrete a soluble factor (or factors) that stimulates progenitor cell activity and, selectively, the osteogenic differentiation of MSCs that could contribute to niche exit.Keywords
This publication has 64 references indexed in Scilit:
- Heparan Sulfate Mediates the Proliferation and Differentiation of Rat Mesenchymal Stem CellsStem Cells and Development, 2009
- A Perivascular Origin for Mesenchymal Stem Cells in Multiple Human OrgansCell Stem Cell, 2008
- IFATS Collection: Adipose Stromal Cell Differentiation Is Reduced by Endothelial Cell Contact and Paracrine Communication: Role of Canonical Wnt SignalingThe International Journal of Cell Cloning, 2008
- The ground state of embryonic stem cell self-renewalNature, 2008
- Age-related changes in human bone marrow-derived mesenchymal stem cells: Consequences for cell therapiesMechanisms of Ageing and Development, 2008
- BioGRID: a general repository for interaction datasetsNucleic Acids Research, 2006
- Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statementCytotherapy, 2006
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- Turning Blood into Brain: Cells Bearing Neuronal Antigens Generated in Vivo from Bone MarrowScience, 2000
- Mammalian Neural Stem CellsScience, 2000