Author contributions: Y.C.L.: design of the study, collection, analysis and interpretation of data, and manuscript writing; S.H.T. and Z.Y.Z.: conception and design of the study and analysis and interpretation of data; M.S.K.C.: conception and design of the study, analysis and interpretation of data, and manuscript writing; E.S.M.L. and R.D.K.: analysis and interpretation of data; C.N.Z.M.: analysis and interpretation of data and manuscript writing; N.K.R.: provision of study material; R.J.M.B.: provision of study material and analysis and interpretation of data; N.M.F.: analysis of data and manuscript writing; M.C.: conception and design of the study, administrative support, and analysis of data; J.K.Y.C.: conception and design, financial support, administrative support, provision of study materials, analysis of data, manuscript writing, and final approval of the manuscript.
Article first published online: 20 AUG 2012
Copyright © 2012 AlphaMed Press
Volume 30, Issue 9, pages 1911–1924, September 2012
How to Cite
Liu, Y., Teoh, S.-H., Chong, M. S. K., Lee, E. S. M., Mattar, C. N. Z., Randhawa, N. K., Zhang, Z.-Y., Medina, R. J., Kamm, R. D., Fisk, N. M., Choolani, M. and Chan, J. K. Y. (2012), Vasculogenic and Osteogenesis-Enhancing Potential of Human Umbilical Cord Blood Endothelial Colony-Forming Cells. STEM CELLS, 30: 1911–1924. doi: 10.1002/stem.1164
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS June 3, 2012.
- Issue published online: 20 AUG 2012
- Article first published online: 20 AUG 2012
- Accepted manuscript online: 3 JUL 2012 07:58AM EST
- Manuscript Accepted: 12 JUN 2012
- Manuscript Received: 31 JAN 2012
- National Medical Research Council of Singapore. Grant Numbers: NMRC/1179/2008, NMRC/1268/2010
- NMRC Clinician Scientist Award. Grant Numbers: CSA/007/2009, CSA/012/2009
- Endothelial progenitor cells;
- Endothelial cell forming cells;
- Mesenchymal stem cells;
Umbilical cord blood-derived endothelial colony-forming cells (UCB-ECFC) show utility in neovascularization, but their contribution to osteogenesis has not been defined. Cocultures of UCB-ECFC with human fetal-mesenchymal stem cells (hfMSC) resulted in earlier induction of alkaline phosphatase (ALP) (Day 7 vs. 10) and increased mineralization (1.9×; p < .001) compared to hfMSC monocultures. This effect was mediated through soluble factors in ECFC-conditioned media, leading to 1.8–2.2× higher ALP levels and a 1.4–1.5× increase in calcium deposition (p < .01) in a dose-dependent manner. Transcriptomic and protein array studies demonstrated high basal levels of osteogenic (BMPs and TGF-βs) and angiogenic (VEGF and angiopoietins) regulators. Comparison of defined UCB and adult peripheral blood ECFC showed higher osteogenic and angiogenic gene expression in UCB-ECFC. Subcutaneous implantation of UCB-ECFC with hfMSC in immunodeficient mice resulted in the formation of chimeric human vessels, with a 2.2-fold increase in host neovascularization compared to hfMSC-only implants (p = .001). We conclude that this study shows that UCB-ECFC have potential in therapeutic angiogenesis and osteogenic applications in conjunction with MSC. We speculate that UCB-ECFC play an important role in skeletal and vascular development during perinatal development but less so in later life when expression of key osteogenesis and angiogenesis genes in ECFC is lower. Stem Cells2012;30:1911–1924