Pharmaceutical Research

, Volume 28, Issue 6, pp 1385–1394

The Effect of Human Bone Marrow Stroma-Derived Heparan Sulfate on the Ex Vivo Expansion of Human Cord Blood Hematopoietic Stem Cells

Authors

  • Diah S. Bramono
    • Stem Cells and Tissue Repair Group, Institute of Medical BiologyA*STAR (Agency for Science, Technology and Research)
  • David A. Rider
    • Stem Cells and Tissue Repair Group, Institute of Medical BiologyA*STAR (Agency for Science, Technology and Research)
  • Sadasivam Murali
    • Stem Cells and Tissue Repair Group, Institute of Medical BiologyA*STAR (Agency for Science, Technology and Research)
  • Victor Nurcombe
    • Stem Cells and Tissue Repair Group, Institute of Medical BiologyA*STAR (Agency for Science, Technology and Research)
    • Stem Cells and Tissue Repair Group, Institute of Medical BiologyA*STAR (Agency for Science, Technology and Research)
    • Department of Orthopaedic Surgery Yong Loo Lin School of MedicineNational University of Singapore
Research Paper

DOI: 10.1007/s11095-010-0352-y

Cite this article as:
Bramono, D.S., Rider, D.A., Murali, S. et al. Pharm Res (2011) 28: 1385. doi:10.1007/s11095-010-0352-y

ABSTRACT

Purpose

In order to address cell dose limitations associated with the use of cord blood hematopoietic stem cell (HSC) transplantation, we explored the effect of bone marrow stroma-derived heparan sulfate (HS) on the ex vivo expansion of HSCs.

Methods

Heparan sulfate was isolated and purified from the conditioned media of human bone marrow stromal cells and used for the expansion of cord blood-derived CD34+ cells in the presence of a cocktail of cytokines.

Results

The number of myeloid lineage-committed progenitor cells was increased at low dosage of HS as illustrated by an increase in the total number of colony-forming cells (CFC) and colonies of erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) precursors. Notably, the stroma-derived HS did not alter the growth of CD34+ HSCs or negatively affect the levels of various HSC phenotypic markers after expansion.

Conclusions

This study shows that HS secreted into solution by stromal cells has the capacity to support hematopoietic cytokines in the maintenance and expansion of HSCs. The incorporation of stroma-derived HS as a reagent may improve the efficacy of cord blood HSC transplantation by enhancing the number of committed cells and accelerating the rate of engraftment.

KEY WORDS

cord bloodglycosaminoglycanhematopoietic stem cellheparan sulfatestem cell expansion

Copyright information

© Springer Science+Business Media, LLC 2010