title: A Glycovariant of Human CD44 is Characteristically Expressed on Human Mesenchymal Stem Cells.
abstract: The clinical effectiveness of systemically administered human mesenchymal stem cells (hMSCs) depends on their capacity to engage vascular endothelium. hMSCs derived from bone marrow (BM-hMSCs) natively lack endothelial binding capacity, but express a CD44 glycovariant containing N-linked sialyllactosamines that can be α(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeXdecorations, thereby creating hematopoietic cell E-/L-selectin ligand (HCELL). HCELL expression programs potent shear-resistant adhesion of circulating cells to endothelial beds expressing E-selectin. An alternative source of hMSCs is adipose tissue (A-hMSCs), and we assessed whether A-hMSCs bind E-selectin and/or possess sialyllactosamine-decorated CD44 accessible to α(1,3)-fucosylation. Similar to BM-hMSCs, we found that A-hMSCs natively lack E-selectin ligands, but FTVI-mediated cell surface α(1,3)-fucosylation induces sLeXexpression and robust E-selectin binding secondary to conversion of CD44 into HCELL. Moreover, treatment with the α(1,3)-fucosyltransferase-FTVII also generated expression of HCELL on both BM-hMSCs and A-hMSCs, with sLeXdecorations created on N-linked glycans of the "standard" CD44 (CD44s) isoform. The finding that hMSCs from both source tissues each lack native E-selectin ligand expression prompted examination of the expression of glycosyltransferases that direct lactosaminyl glycan synthesis. These studies reveal that both types of hMSCs conspicuously lack transcripts encoding α(1,3)-fucosyltransferases, but equally express glycosyltransferases critical to creation of sialyllactosamines. Collectively, these data indicate that assembly of a sialyllactosaminyl-decorated CD44s glycovariant is a conserved feature of hMSCs derived from adipose tissue and marrow, thus identifying a CD44 glycosignature of these cells and supporting the applicability of cell surface α(1,3)-fucosylation in programming migration of systemically administered A-hMSCs to sites of tissue injury/inflammation. Stem Cells 2017;35:1080-1092.
authors.affiliation: Department of Dermatology, and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Program of Excellence in Glycosciences, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Gisela
authors.initials: G
authors.lastname: Pachón-Peña
authors.affiliation: Department of Dermatology, and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Program of Excellence in Glycosciences, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Conor
authors.initials: C
authors.lastname: Donnelly
authors.affiliation: Department of Dermatology, and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Program of Excellence in Glycosciences, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Catalina
authors.initials: C
authors.lastname: Ruiz-Cañada
authors.affiliation: Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Florida College of Medicine, Gainesville, Florida, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Katz
authors.affiliation: Hospital Universitario de Tarragona Joan XXIII. Institut d'Investigació Sanitària Pere Virgili Universitat Rovira i Virgili, Tarragona, Spain.|CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Fernández-Veledo
authors.affiliation: Hospital Universitario de Tarragona Joan XXIII. Institut d'Investigació Sanitària Pere Virgili Universitat Rovira i Virgili, Tarragona, Spain.|CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Vendrell
authors.affiliation: Department of Dermatology, and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Program of Excellence in Glycosciences, Harvard Medical School, Boston, Massachusetts, USA.|Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Sackstein
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology; D002448:Cell Adhesion; D002454:Cell Differentiation; D002460:Cell Line; D019040:E-Selectin / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism; D006031:Glycosylation; D016695:Glycosyltransferases / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D016130:Immunophenotyping; D019041:L-Selectin / Q000378:metabolism; D008024:Ligands; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009439:Neuraminidase / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism; D011485:Protein Binding
chemical_list: C497483:CD44 protein, human; D019040:E-Selectin; D005353:Fibronectins; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D008024:Ligands; D011134:Polysaccharides; D019041:L-Selectin; D016695:Glycosyltransferases; D009439:Neuraminidase
keywords: E-selectin ligand; Exofucosylation; Fucosyltransferase; Glycosyltransferase-programmed stereosubstitution; Hematopoietic cell E-/L-selectin ligand; Mesenchymal stem cell; Sialyl Lewis X; sLeX