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 Blood, 15 November 2004, Vol. 104, No. 10, pp. 3091-3096.
Prepublished online as a Blood First Edition Paper on July 27, 2004; DOI 10.1182/blood-2004-02-0650.

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HEMATOPOIESIS

Surface fucosylation of human cord blood cells augments binding to P-selectin and E-selectin and enhances engraftment in bone marrow

Lijun Xia, J. Michael McDaniel, Tadayuki Yago, Andrea Doeden, and Rodger P. McEver

From the Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK; Renaissance Women's Hospital of Edmond, Edmond, OK; and the Department of Biochemistry and Molecular Biology and Oklahoma Center for Medical Glycobiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.

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 {alpha}1-3 fucosylated to form glycan determinants such as sialyl Lewis x (sLex). We found that inadequate {alpha}1-3 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 {alpha}1-3 fucosyltransferase VI increased cell-surface sLex 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 {alpha}1-3 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.


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Glycosylation engineering enhances stem cell homing
Ajit Varki
Blood 2004 104: 3005. [Full Text] [PDF]



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