Enforced fucosylation of neonatal CD34+ cells generates selectin ligands that enhance the initial interactions with microvessels but not homing to bone marrow

Andrés Hidalgo, Paul S. Frenette

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Hematopoietic progenitor/stem cell homing to the bone marrow requires the concerted action of several adhesion molecules. Endothelial P- and E-selectins play an important role in this process, but their ligands on a large subset of neonate-derived human CD34+ cells are absent, leading to a reduced ability to interact with the bone marrow (BM) microvasculature. We report here that this deficiency results from reduced α1,3-fucosyltransferase (FucT) expression and activity in these CD34+ cells. Incubation of CD34 + cells with recombinant human FucTVI rapidly corrected the deficiency in nonbinding CD34+ cells and further increased the density of ligands for both P- and E-selectins on all cord blood-derived CD34+ cells. Intravital microscopy studies revealed that these FucTVI-treated CD34+ cells displayed a marked enhancement in their initial interactions with the BM microvasculature, but unexpectedly, homing into the BM was not improved by FucTVI treatment. These data indicate that, although exogenous FucT enzyme activity can rapidly modulate selectin binding avidity of cord blood CD34+ cells, further studies are needed to understand how to translate a positive effect on progenitor cell adhesion in bone marrow microvessels into one that significantly influences migration and lodgement into the parenchyma.

Original languageEnglish (US)
Pages (from-to)567-575
Number of pages9
JournalBlood
Volume105
Issue number2
DOIs
StatePublished - Jan 15 2005
Externally publishedYes

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Selectins
Microvessels
Bone
Bone Marrow
Ligands
P-Selectin
E-Selectin
galactoside 3-fucosyltransferase
Hematopoietic Stem Cells
Fetal Blood
Blood
Fucosyltransferases
Cell adhesion
Enzyme activity
Stem cells
Cell Adhesion
Adhesion
Blood Cells
Stem Cells
Molecules

ASJC Scopus subject areas

  • Hematology

Cite this

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abstract = "Hematopoietic progenitor/stem cell homing to the bone marrow requires the concerted action of several adhesion molecules. Endothelial P- and E-selectins play an important role in this process, but their ligands on a large subset of neonate-derived human CD34+ cells are absent, leading to a reduced ability to interact with the bone marrow (BM) microvasculature. We report here that this deficiency results from reduced α1,3-fucosyltransferase (FucT) expression and activity in these CD34+ cells. Incubation of CD34 + cells with recombinant human FucTVI rapidly corrected the deficiency in nonbinding CD34+ cells and further increased the density of ligands for both P- and E-selectins on all cord blood-derived CD34+ cells. Intravital microscopy studies revealed that these FucTVI-treated CD34+ cells displayed a marked enhancement in their initial interactions with the BM microvasculature, but unexpectedly, homing into the BM was not improved by FucTVI treatment. These data indicate that, although exogenous FucT enzyme activity can rapidly modulate selectin binding avidity of cord blood CD34+ cells, further studies are needed to understand how to translate a positive effect on progenitor cell adhesion in bone marrow microvessels into one that significantly influences migration and lodgement into the parenchyma.",
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