A Glycovariant of Human CD44 Is Characteristically Expressed on Human Mesenchymal Stem Cells

Author, as appears in the article.: Pachon-Pena, Gisela; Donnelly, Conor; Ruiz-Canada, Catalina; Katz, Adam; Fernandez-Veledo, Sonia; Vendrell, Joan; Sackstein, Robert

Department: Medicina i Cirurgia; Ciències Mèdiques Bàsiques

URV's Author/s: Fernandez Veledo, Sonia / Vendrell Ortega, Juan José

Keywords: Stromal cells; Slex; Sle(x); Sle x; Sialyl lewis x; Protein binding; Polysaccharides; Neuraminidase; Mesenchymal stem cells; Mesenchymal stem cell; Ligands; L-selectin; Immunophenotyping; Hyaluronan receptors; Humans; Hematopoietic cell e-/l-selectin ligand; Hematopoietic cell e-/ l-selectin ligand; Glycosyltransferases; Glycosyltransferase-programmed stereosubstitution; Glycosylation; Glycoproteins; Gene expression regulation; Fucosyltransferase; Fucosyl-transferases; Fibronectins; Exofucosylation; E-selectin ligands; E-selectin ligand; E-selectin; Cell line; Cell differentiation; Cell adhesion; Cd44 protein, human; Bone marrow cells; Adipose tissue; sialyl lewis x; mesenchymal stem cell; hematopoietic cell e-/l-selectin ligand; glycosyltransferase-programmed stereosubstitution; fucosyltransferase; exofucosylation; e-selectin ligand

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 sLeX decorations, 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 sLeX expression 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 sLeX decorations 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.

Thematic Areas: Oncology; Nutrição; Molecular medicine; Medicine (miscellaneous); Medicine (all); Medicina veterinaria; Medicina ii; Medicina i; Interdisciplinar; Hematology; General medicine; Farmacia; Engenharias ii; Educação física; Developmental biology; Ciências biológicas iii; Ciências biológicas ii; Ciências biológicas i; Cell biology; Cell & tissue engineering; Biotecnología; Biotechnology & applied microbiology

licence for use: https://creativecommons.org/licenses/by/3.0/es/

ISSN: 15494918

Author's mail: sonia.fernandez@urv.cat; jvortega@iispv.cat

Record's date: 2025-03-03

Paper version: info:eu-repo/semantics/acceptedVersion

Link to the original source: https://stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/stem.2549

Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/

Paper original source: Stem Cells. 35 (4): 1080-1092

APA: Pachon-Pena, Gisela; Donnelly, Conor; Ruiz-Canada, Catalina; Katz, Adam; Fernandez-Veledo, Sonia; Vendrell, Joan; Sackstein, Robert (2017). A Glycovariant of Human CD44 Is Characteristically Expressed on Human Mesenchymal Stem Cells. Stem Cells, 35(4), 1080-1092. DOI: 10.1002/stem.2549

Article's DOI: 10.1002/stem.2549

Entity: Universitat Rovira i Virgili

Journal publication year: 2017

Publication Type: Journal Publications