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Regenerative Medicine

Vasculogenic and Osteogenesis-Enhancing Potential of Human Umbilical Cord Blood Endothelial Colony-Forming Cells†‡§

  1. Yuchun Liu1,2,
  2. Swee-Hin Teoh3,†,
  3. Mark S. K. Chong1,†,
  4. Eddy S. M. Lee1,4,†,
  5. Citra N. Z. Mattar1,†,
  6. Nau'shil Kaur Randhawa1,†,
  7. Zhi-Yong Zhang1,2,†,
  8. Reinhold J. Medina5,†,
  9. Roger D. Kamm6,†,
  10. Nicholas M. Fisk1,7,†,
  11. Mahesh Choolani1,†,
  12. Jerry K. Y. Chan1,8,9,†,¶,*

Article first published online: 20 AUG 2012

DOI: 10.1002/stem.1164

Issue

STEM CELLS

STEM CELLS

Volume 30, Issue 9, pages 1911–1924, September 2012

Additional Information

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

Author Information

  1. 1

    Experimental Fetal Medicine Group, Department of Obstetrics and Gynaecology, Yong Loo Lin School of MedicineNational University of Singapore, Singapore

  2. 2

    BIOMAT, Department of Mechanical Engineering, Faculty of Engineering, National University of Singapore, Singapore

  3. 3

    Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore

  4. 4

    Richard M. Lucas Center for Imaging, Department of Radiology, Stanford University, California, USA

  5. 5

    Centre for Vision and Vascular Science, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Royal Victoria Hospital, Belfast, United Kingdom

  6. 6

    Department of Biological and Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, United States of America and Singapore-MIT Alliance for Research & Technology, Singapore

  7. 7

    UQ Centre for Clinical Research, University of Queensland, Herston Campus, Brisbane, Australia

  8. 8

    Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore

  9. 9

    Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore

  1. †

    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.

  2. Telephone: 65-6772-2672; Fax: 65-6779-4753

*Experimental Fetal Medicine Group, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore

  1. †

    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.

  2. ‡

    Disclosure of potential conflicts of interest is found at the end of this article.

  3. §

    First published online in STEM CELLSEXPRESS June 3, 2012.

  4. Telephone: 65-6772-2672; Fax: 65-6779-4753

Publication History

  1. Issue published online: 20 AUG 2012
  2. Article first published online: 20 AUG 2012
  3. Accepted manuscript online: 3 JUL 2012 07:58AM EST
  4. Manuscript Accepted: 12 JUN 2012
  5. Manuscript Received: 31 JAN 2012

Funded by

  • 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

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Keywords:

  • Endothelial progenitor cells;
  • Endothelial cell forming cells;
  • Mesenchymal stem cells;
  • Osteogenesis;
  • Vasculogenesis

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. Stem Cells2012;30:1911–1924

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