Fucosyltransferase VII improves the function of selectin ligands on cord blood hematopoietic stem cells

摘要

Selectins and their carbohydrate ligands mediate the homing of hematopoietic stem/progenitor cells (HSPCs) to the bone marrow. We have previously shown that ex vivo fucosylation of selectin ligands on HSPCs by α1,3 fucosyltransferase VI (FUT6) leads to improved human cord blood (CB)-HSPC engraftment in non-obese diabetic (NOD)/severe combined immune deficient (SCID) mice. In the present study, we determined whether surface fucosylation with α1,3 fucosyltransferase VII (FUT7), which is primarily expressed by hematopoietic cells, improves the function of selectin ligands on CB-HSPCs in comparison with FUT6. A saturating amount of either FUT6 or FUT7, which generates comparable levels of expression of fucosylated epitopes on CB CD34⁺ cells, was used for these experiments. In vitro, FUT7-treated CB CD34⁺ cells exhibited greater binding to P- or E-selectin than that of FUT6-treated CB CD34⁺ cells under static or physiological flow conditions. In vivo, FUT7 treatment, like FUT6, improved the early engraftment of CB CD34⁺ cells in the bone marrow of sublethally irradiated NOD/SCID interleukin (IL)-2Rγ^null (NSG) mice. FUT7 also exhibited marginally—yet statistically significant—increased engraftment at 4 and 6 weeks after transplantation. In addition, FUT7-treated CB CD34⁺ cells exhibited increased homing to the bone marrow of irradiated NSG mice relative to sham-treated cells. These data indicate that FUT7 is effective at improving the function of selectin ligands on CB-HSPCs in vitro and enhancing early engraftment of treated CB-HSPCs in the bone marrow of recipients.