Surface fucosylation of human cord blood cells augments binding to P-selectin and E-selectin and enhances engraftment in bone marrow.
Murine hematopoietic stem and progenitor cells (HSPCs) home to bone marrow in part by rolling on P-selectin and E-selectin expressed on endothelial cells. Human adult CD34(+) cells, which are enriched in HSPCs, roll on endothelial selectins in bone marrow vessels of nonobese diabetic/severe combined immune deficiency (NOD/SCID) mice. Many human umbilical cord blood (CB) CD34(+) cells do not roll in these vessels, in part because of an uncharacterized defect in binding to P-selectin. Selectin ligands must be alpha1-3 fucosylated to form glycan determinants such as sialyl Lewis x (sLe(x)). We found that inadequate alpha1-3 fucosylation of CB CD34(+) cells, particularly CD34(+)CD38(-/low) cells that are highly enriched in HSPCs, caused them to bind poorly to E-selectin as well as to P-selectin. Treatment of CB CD34(+) cells with guanosine diphosphate (GDP) fucose and exogenous alpha1-3 fucosyltransferase VI increased cell-surface sLe(x) determinants, augmented binding to fluid-phase P- and E-selectin, and improved cell rolling on P- and E-selectin under flow. Similar treatment of CB mononuclear cells enhanced engraftment of human hematopoietic cells in bone marrows of irradiated NOD/SCID mice. These observations suggest that alpha1-3 fucosylation of CB cells might be a simple and effective method to improve hematopoietic cell homing to and engraftment in bone marrows of patients receiving CB transplants.
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA. lijun-xia@omrf.ouhsc.edu.
Lijun
L
Xia
J Michael
JM
McDaniel
Tadayuki
T
Yago
Andrea
A
Doeden
Rodger P
RP
McEver
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002448:Cell Adhesion; D019040:E-Selectin / Q000378:metabolism*; D000939:Epitopes; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D005643:Fucose / Q000378:metabolism*; D005647:Fucosyltransferases / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D036904:Leukocyte Rolling; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D016256:Lewis X Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D019007:P-Selectin / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms
D018952:Antigens, CD34; D019040:E-Selectin; D000939:Epitopes; D016256:Lewis X Antigen; D019007:P-Selectin; D005643:Fucose; D005647:Fucosyltransferases; C019818:3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase