Vasculogenic and osteogenesis-enhancing potential of human umbilical cord blood endothelial colony-forming cells

Liu, Yuchun, Teoh, Swee-Hin, Chong, Mark S. K., Lee, Eddy S. M., Mattar, Citra N. Z., Randhawa, Nau'shil Kaur, Zhang, Zhi-Yong, Medina, Reinhold J., Kamm, Roger D., Fisk, Nicholas M., Choolani, Mahesh and Chan, Jerry K. Y. (2012) Vasculogenic and osteogenesis-enhancing potential of human umbilical cord blood endothelial colony-forming cells. Stem Cells, 30 9: 1911-1924.


Author Liu, Yuchun
Teoh, Swee-Hin
Chong, Mark S. K.
Lee, Eddy S. M.
Mattar, Citra N. Z.
Randhawa, Nau'shil Kaur
Zhang, Zhi-Yong
Medina, Reinhold J.
Kamm, Roger D.
Fisk, Nicholas M.
Choolani, Mahesh
Chan, Jerry K. Y.
Title Vasculogenic and osteogenesis-enhancing potential of human umbilical cord blood endothelial colony-forming cells
Journal name Stem Cells  (ERA 2012 Listed)    (ERA 2010 Rank A*)   Check publisher's open access policy
Publication date 2012-09
Sub-type Article
DOI 10.1002/stem.1164
Volume number 30
Issue number 9
ISSN 1066-5099; 1549-4918
Start page 1911
End page 1924
Total pages 14
Place of publication Durham, NC, United States
Publisher AlphaMed Press
Collection year 2013
Language eng
Formatted abstract 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.
Keyword Endothelial progenitor cells
Endothelial cell forming cells
Mesenchymal stem cells
Osteogenesis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article
Collections: UQ Centre for Clinical Research Publications
Official 2013 Collection
 
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