Cell surface glycan engineering of neural stem cells augments neurotropism and improves recovery in a murine model of multiple sclerosis
dc.contributor.author | Merzaban, Jasmeen | |
dc.contributor.author | Imitola, Jaime | |
dc.contributor.author | Starossom, Sarah C. | |
dc.contributor.author | Zhu, Bing | |
dc.contributor.author | Wang, Yue | |
dc.contributor.author | Lee, Jack | |
dc.contributor.author | Ali, Amal J. | |
dc.contributor.author | Olah, Marta | |
dc.contributor.author | AbuElela, Ayman | |
dc.contributor.author | Khoury, Samia J. | |
dc.contributor.author | Sackstein, Robert | |
dc.date.accessioned | 2017-01-02T09:28:27Z | |
dc.date.available | 2017-01-02T09:28:27Z | |
dc.date.issued | 2015-07-07 | |
dc.identifier.citation | Merzaban JS, Imitola J, Starossom SC, Zhu B, Wang Y, et al. (2015) Cell surface glycan engineering of neural stem cells augments neurotropism and improves recovery in a murine model of multiple sclerosis. Glycobiology 25: 1392–1409. Available: http://dx.doi.org/10.1093/glycob/cwv046. | |
dc.identifier.issn | 0959-6658 | |
dc.identifier.issn | 1460-2423 | |
dc.identifier.pmid | 26153105 | |
dc.identifier.doi | 10.1093/glycob/cwv046 | |
dc.identifier.uri | http://hdl.handle.net/10754/622382 | |
dc.description.abstract | Neural stem cell (NSC)-based therapies offer potential for neural repair in central nervous system (CNS) inflammatory and degenerative disorders. Typically, these conditions present with multifocal CNS lesions making it impractical to inject NSCs locally, thus mandating optimization of vascular delivery of the cells to involved sites. Here, we analyzed NSCs for expression of molecular effectors of cell migration and found that these cells are natively devoid of E-selectin ligands. Using glycosyltransferase-programmed stereosubstitution (GPS), we glycan engineered the cell surface of NSCs ("GPS-NSCs") with resultant enforced expression of the potent E-selectin ligand HCELL (hematopoietic cell E-/L-selectin ligand) and of an E-selectin-binding glycoform of neural cell adhesion molecule ("NCAM-E"). Following intravenous (i.v.) injection, short-term homing studies demonstrated that, compared with buffer-treated (control) NSCs, GPS-NSCs showed greater neurotropism. Administration of GPS-NSC significantly attenuated the clinical course of experimental autoimmune encephalomyelitis (EAE), with markedly decreased inflammation and improved oligodendroglial and axonal integrity, but without evidence of long-term stem cell engraftment. Notably, this effect of NSC is not a universal property of adult stem cells, as administration of GPS-engineered mouse hematopoietic stem/progenitor cells did not improve EAE clinical course. These findings highlight the utility of cell surface glycan engineering to boost stem cell delivery in neuroinflammatory conditions and indicate that, despite the use of a neural tissue-specific progenitor cell population, neural repair in EAE results from endogenous repair and not from direct, NSC-derived cell replacement. | |
dc.description.sponsorship | This effort was supported by National Institutes of Health grants PO1 HL107146 [NHLBI Program of Excellence in Glycosciences (R.S.)], RO1 HL73714 (R.S.), RO1 HL60528 (R.S.), AI043496 (S.J.K.) and AI071448 (S.J.K.). This work was also supported by the Edward and Dana Slatkin Research Fund and the Brourman Family Fund (R.S.), and by a National Multiple Sclerosis Society grant RG3945 (S.J.K). The King Abdullah University of Science and Technology Faculty Baseline Research Funding Program (J.S.M.) also supported this work. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. | |
dc.publisher | Oxford University Press (OUP) | |
dc.subject | Exofucosylation | |
dc.subject | Glycan engineering | |
dc.subject | HCELL | |
dc.subject | Multiple sclerosis | |
dc.subject | Neural stem cell | |
dc.title | Cell surface glycan engineering of neural stem cells augments neurotropism and improves recovery in a murine model of multiple sclerosis | |
dc.type | Article | |
dc.contributor.department | Biological and Environmental Sciences and Engineering (BESE) Division | |
dc.contributor.department | Bioscience Program | |
dc.identifier.journal | Glycobiology | |
dc.identifier.pmcid | PMC4634313 | |
dc.contributor.institution | Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, United States | |
dc.contributor.institution | Department of Neurology, Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, United States | |
dc.contributor.institution | Laboratory for Neural Stem Cells and Functional Neurogenetics, Division of Neuroimmunology and Multiple Sclerosis, Departments of Neurology and Neuroscience, Ohio State University Wexner Medical Center, Biomedical Research Tower, Room 688. 460 W. 12th Avenue, Columbus, OH, 43210, United States | |
dc.contributor.institution | Institute for Medical Immunology, Charite University Medicine Berlin, Berlin, Germany | |
dc.contributor.institution | Abu Haidar Neuroscience Institute, American University of Beirut Medical Center, Beirut, Lebanon | |
dc.contributor.institution | Department of Medicine, Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, United States | |
kaust.person | Merzaban, Jasmeen S. | |
kaust.person | Ali, Amal J. | |
kaust.person | AbuElela, Ayman | |
dc.date.published-online | 2015-07-07 | |
dc.date.published-print | 2015-12 |
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