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J Clin Invest. 2013 Aug;123(8):3420-35. doi: 10.1172/JCI64060. Epub 2013 Jul 25.

The nucleotide sugar UDP-glucose mobilizes long-term repopulating primitive hematopoietic cells.

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1
University of Pittsburgh Cancer Institute and Department of Medicine, Division of Hematology and Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.

Abstract

Hematopoietic stem progenitor cells (HSPCs) are present in very small numbers in the circulating blood in steady-state conditions. In response to stress or injury, HSPCs are primed to migrate out of their niche to peripheral blood. Mobilized HSPCs are now commonly used as stem cell sources due to faster engraftment and reduced risk of posttransplant infection. In this study, we demonstrated that a nucleotide sugar, UDP-glucose, which is released into extracellular fluids in response to stress, mediates HSPC mobilization. UDP-glucose-mobilized cells possessed the capacity to achieve long-term repopulation in lethally irradiated animals and the ability to differentiate into multi-lineage blood cells. Compared with G-CSF-mobilized cells, UDP-glucose-mobilized cells preferentially supported long-term repopulation and exhibited lymphoid-biased differentiation, suggesting that UDP-glucose triggers the mobilization of functionally distinct subsets of HSPCs. Furthermore, co-administration of UDP-glucose and G-CSF led to greater HSPC mobilization than G-CSF alone. Administration of the antioxidant agent NAC significantly reduced UDP-glucose-induced mobilization, coinciding with a reduction in RANKL and osteoclastogenesis. These findings provide direct evidence demonstrating a potential role for UDP-glucose in HSPC mobilization and may provide an attractive strategy to improve the yield of stem cells in poor-mobilizing allogeneic or autologous donors.

PMID:
23863713
PMCID:
PMC3726149
DOI:
10.1172/JCI64060
[Indexed for MEDLINE]
Free PMC Article

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