Blood, 15 March 2003, Vol. 101, No. 6, pp. 2243-2245
HEMATOPOIESIS
Brief report
Identification of an MIP-1
-binding heparan sulfate
oligosaccharide that supports long-term in vitro maintenance of
human LTC-ICs
Sally E. Stringer,
Matthew
S. Nelson, and
Pankaj Gupta
From the Paterson Institute for Cancer Research,
Manchester, United Kingdom; the Hematology-Oncology Section, VA Medical
Center, and the Division of Hematology-Oncology-Transplantation,
Department of Medicine, University of Minnesota Medical School,
Minneapolis.
We previously showed that heparan sulfate (HS) is required for in
vitro cytokine + chemokine-mediated maintenance of primitive human
hematopoietic progenitors. However, HS preparations are mixtures of
polysaccharide chains of varying size, structure, and protein-binding
abilities. Therefore, we examined whether the long-term
culture-initiating cells (LTC-IC) supportive capability of HS is
attributable to an oligosaccharide of defined length and
protein-binding ability. Oligosaccharides of a wide range of sizes were
prepared, and their capability to support human marrow LTC-IC
maintenance in the presence of low-dose cytokines and a single
chemokine, macrophage inflammatory protein-1
(MIP-1), was
examined. LTC-IC supportive capability of HS oligosaccharides correlated directly with size and MIP-1 binding ability. A
specific MIP-1-binding HS oligosaccharide
preparation of Mr 10 kDa that optimally supported
LTC-IC maintenance was identified. This oligosaccharide had the
structure required for MIP-1 binding, which we have recently described. The present study defines the minimum size and structural features of LTC-IC supportive HS.
