title: Cell surface glycoengineering improves selectin-mediated adhesion of mesenchymal stem cells (MSCs) and cardiosphere-derived cells (CDCs): Pilot validation in porcine ischemia-reperfusion model.
abstract: Promising results are emerging in clinical trials focused on stem cell therapy for cardiology applications. However, the low homing and engraftment of the injected cells to target tissue continues to be a problem. Cellular glycoengineering can address this limitation by enabling the targeting of stem cells to sites of vascular injury/inflammation. Two such glycoengineering methods are presented here: i. The non-covalent incorporation of a P-selectin glycoprotein ligand-1 (PSGL-1) mimetic 19Fc[FUT7(+)] via lipid-protein G fusion intermediates that intercalate onto the cell surface, and ii. Over-expression of the α(1,3)fucosyltransferse FUT7 in cells. Results demonstrate the efficient coupling of 19Fc[FUT7(+)] onto both cardiosphere-derived cells (CDCs) and mesenchymal stem cells (MSCs), with coupling being more efficient when using protein G fused to single-tailed palmitic acid rather than double-tailed DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine). This non-covalent cellular modification was mild since cell proliferation and stem-cell marker expression was unaltered. Whereas coupling using 19Fc[FUT7(+)] enhanced cell capture on recombinant P-selectin or CHO-P cell surfaces, α(1,3)fucosylation was necessary for robust binding to E-selectin and inflamed endothelial cells under shear. Pilot studies confirm the safety and homing efficacy of the modified stem cells to sites of ischemia-reperfusion in the porcine heart. Overall, glycoengineering with physiological selectin-ligands may enhance stem cell engraftment.
authors.affiliation: Department of Chemical and Biological Engineering, The State University of New York, 906 Furnas Hall, Buffalo, NY 14260, USA; Department of Anesthesiology, The State University of New York, 252 Farber Hall, Buffalo, NY 14214, USA; Division of Cardiovascular Medicine, The State University of New York, Clinical Translational Research Center, 875 Ellicott Street, Buffalo, NY 14203, USA.
authors.forename: Chi Y
authors.initials: CY
authors.lastname: Lo
authors.affiliation: Division of Cardiovascular Medicine, The State University of New York, Clinical Translational Research Center, 875 Ellicott Street, Buffalo, NY 14203, USA.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Weil
authors.affiliation: Division of Cardiovascular Medicine, The State University of New York, Clinical Translational Research Center, 875 Ellicott Street, Buffalo, NY 14203, USA.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Palka
authors.affiliation: Department of Chemical and Biological Engineering, The State University of New York, 906 Furnas Hall, Buffalo, NY 14260, USA.
authors.forename: Arezoo
authors.initials: A
authors.lastname: Momeni
authors.affiliation: Division of Cardiovascular Medicine, The State University of New York, Clinical Translational Research Center, 875 Ellicott Street, Buffalo, NY 14203, USA; VA Western New York Health Care System, Buffalo, NY 14215, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Canty
authors.affiliation: Department of Chemical and Biological Engineering, The State University of New York, 906 Furnas Hall, Buffalo, NY 14260, USA; The NY State Center for Excellence in Bioinformatics and Life Sciences, The State University of New York, 701 Ellicott St., Buffalo, NY 14203, USA. Electronic address: neel@buffalo.edu.
authors.forename: Sriram
authors.initials: S
authors.lastname: Neelamegham
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005647:Fucosyltransferases / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology*; D010865:Pilot Projects; D015427:Reperfusion Injury / Q000628:therapy*; D019087:Selectins / Q000502:physiology*; D013552:Swine
chemical_list: D006023:Glycoproteins; D019087:Selectins; D005647:Fucosyltransferases
keywords: Adhesion molecule; Blood flow; Cell adhesion; Mesenchymal stem cells; PSGL-1; Recombinant protein; Selectin; Sialyl Lewis-X