Research Paper

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

  • Diah S. BramonoAffiliated withStem Cells and Tissue Repair Group, Institute of Medical Biology, A*STAR (Agency for Science, Technology and Research)
  • , David A. RiderAffiliated withStem Cells and Tissue Repair Group, Institute of Medical Biology, A*STAR (Agency for Science, Technology and Research)
  • , Sadasivam MuraliAffiliated withStem Cells and Tissue Repair Group, Institute of Medical Biology, A*STAR (Agency for Science, Technology and Research)
  • , Victor NurcombeAffiliated withStem Cells and Tissue Repair Group, Institute of Medical Biology, A*STAR (Agency for Science, Technology and Research)
  • , Simon M. CoolAffiliated withStem Cells and Tissue Repair Group, Institute of Medical Biology, A*STAR (Agency for Science, Technology and Research)Department of Orthopaedic Surgery Yong Loo Lin School of Medicine, National University of Singapore Email author 

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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 blood glycosaminoglycan hematopoietic stem cell heparan sulfate stem cell expansion