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Review
. 2012 Apr;1253(1):193-200.
doi: 10.1111/j.1749-6632.2011.06421.x. Epub 2012 Feb 21.

Engineering cellular trafficking via glycosyltransferase-programmed stereosubstitution

Robert Sackstein  1
Affiliations
Review

Engineering cellular trafficking via glycosyltransferase-programmed stereosubstitution

Robert Sackstein. Ann N Y Acad Sci. 2012 Apr.

Abstract

The proximate hurdle for cell trafficking to any anatomic site is the initial attachment of circulating cells to target tissue endothelium with sufficient strength to overcome prevailing forces of blood flow. E-selectin, an endothelial molecule that is inducibly expressed at all sites of inflammation, is a potent effector of this primary braking process. This molecule is a member of a family of C-type lectins known as selectins that bind sialofucosylated glycans displayed on either a protein (i.e., glycoprotein) or lipid (i.e., glycolipid) scaffold. On human cells, the predominant E-selectin ligand is a specialized glycoform of CD44 known as hematopoietic cell E-/L-selectin ligand (HCELL). This review focuses on the biology of HCELL/E-selectin interactions in cell migration, and discusses the utility and applicability of glycosyltransferase-programmed stereosubstitution (GPS) for glycoengineering HCELL expression. Without compromising cell viability or native phenotype, this exoglycosylation technology literally "sweetens" CD44, licensing E-selectin-dependent vascular delivery for all cell-based therapeutics.

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Conflict of interest statement

RS’s ownership interests were reviewed and are managed by the Brigham & Women’s Hospital and Partners HealthCare in accordance with their conflict of interest policy.

Figures

Figure 1
Figure 1
Structure of sialylated Lewis X (sLex). Schematic depiction of the canonical selectin binding determinant, sLex (see box), showing linkages of relevant monosaccharide units. Color key figures correspond to respective monosaccharides. The disaccharide unit consisting of galactose and N-acetylglucosamine is known as a “lactosamine” unit. In sLex, the lactosamine is capped with a sialic acid in a(2,3)-linkage to galactose; this structure is known as a “sialyllactosamine” unit. By definition, theβ(1,4)-linkage between galactose and N-acetylglucosamine classifies the lactosamine unit as “type 2”. The sLex structure is a terminal type 2 sialyllactosamine unit containing fucose in α(1,3)-linkage to N-acetylglucosamine.
Figure 2
Figure 2
Application of glycosyltransferase-programmed stereosubstitution (GPS) to enforce HCELL expression. Cell surface CD44 can be converted to the HCELL glycoform by glycan engineering via GPS. In both MSC and HSPC, native CD44 displays type 2 sialyllactactosaminyl glycans; color key figures correspond to respective monosaccharides (for details, see Fig. 1). Ex vivo treatment of cells with fucosyltransferase VI (FTVI) drives α(1,3)-fucosylation of CD44 glycans, thereby generating sLex and, accordingly, HCELL.
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References

    1. Bernardo ME, Locatelli F, Fibbe WE. Mesenchymal stromal cells. Ann N Y Acad Sci. 2009;1176:101–17. - PubMed
    1. Sackstein R. Glycosyltransferase-programmed stereosubstitution (GPS) to create HCELL: engineering a roadmap for cell migration. Immunol Rev. 2009;230:51–74. - PMC - PubMed
    1. Lawrence MB, et al. Threshold levels of fluid shear promote leukocyte adhesion through selectins (CD62L,P,E) J Cell Biol. 1997;136:717–27. - PMC - PubMed
    1. Sackstein R. The lymphocyte homing receptors: gatekeepers of the multistep paradigm. Curr Opin Hematol. 2005;12:444–50. - PubMed
    1. Li Y, et al. ADAM17 deficiency by mature neutrophils has differential effects on L-selectin shedding. Blood. 2006;108:2275–9. - PMC - PubMed

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