The effect of human bone marrow stroma-derived heparan sulfate on the ex vivo expansion of human cord blood hematopoietic stem cells.

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.