Cell surface glycan engineering of neural stem cells augments neurotropism and improves recovery in a murine model of multiple sclerosis

Handle URI:
http://hdl.handle.net/10754/622382
Title:
Cell surface glycan engineering of neural stem cells augments neurotropism and improves recovery in a murine model of multiple sclerosis
Authors:
Merzaban, Jasmeen S. ( 0000-0002-7276-2907 ) ; Imitola, Jaime; Starossom, Sarah C.; Zhu, Bing; Wang, Yue; Lee, Jack; Ali, Amal Jehad Mohammad; Olah, Marta; AbuElela, Ayman ( 0000-0002-4529-3156 ) ; Khoury, Samia J.; Sackstein, Robert
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.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
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.
Publisher:
Oxford University Press (OUP)
Journal:
Glycobiology
Issue Date:
13-Sep-2015
DOI:
10.1093/glycob/cwv046
PubMed ID:
26153105
PubMed Central ID:
PMC4634313
Type:
Article
ISSN:
0959-6658; 1460-2423
Sponsors:
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.
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorMerzaban, Jasmeen S.en
dc.contributor.authorImitola, Jaimeen
dc.contributor.authorStarossom, Sarah C.en
dc.contributor.authorZhu, Bingen
dc.contributor.authorWang, Yueen
dc.contributor.authorLee, Jacken
dc.contributor.authorAli, Amal Jehad Mohammaden
dc.contributor.authorOlah, Martaen
dc.contributor.authorAbuElela, Aymanen
dc.contributor.authorKhoury, Samia J.en
dc.contributor.authorSackstein, Roberten
dc.date.accessioned2017-01-02T09:28:27Z-
dc.date.available2017-01-02T09:28:27Z-
dc.date.issued2015-09-13en
dc.identifier.citationMerzaban 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.en
dc.identifier.issn0959-6658en
dc.identifier.issn1460-2423en
dc.identifier.pmid26153105en
dc.identifier.doi10.1093/glycob/cwv046en
dc.identifier.urihttp://hdl.handle.net/10754/622382-
dc.description.abstractNeural 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.en
dc.description.sponsorshipThis 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.en
dc.publisherOxford University Press (OUP)en
dc.subjectExofucosylationen
dc.subjectGlycan engineeringen
dc.subjectHCELLen
dc.subjectMultiple sclerosisen
dc.subjectNeural stem cellen
dc.titleCell surface glycan engineering of neural stem cells augments neurotropism and improves recovery in a murine model of multiple sclerosisen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalGlycobiologyen
dc.identifier.pmcidPMC4634313en
dc.contributor.institutionDepartment of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, United Statesen
dc.contributor.institutionDepartment of Neurology, Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, United Statesen
dc.contributor.institutionLaboratory 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 Statesen
dc.contributor.institutionInstitute for Medical Immunology, Charite University Medicine Berlin, Berlin, Germanyen
dc.contributor.institutionAbu Haidar Neuroscience Institute, American University of Beirut Medical Center, Beirut, Lebanonen
dc.contributor.institutionDepartment of Medicine, Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, United Statesen
kaust.authorMerzaban, Jasmeen S.en
kaust.authorAli, Amal Jehad Mohammaden
kaust.authorAbuElela, Aymanen

Related articles on PubMed

All Items in KAUST are protected by copyright, with all rights reserved, unless otherwise indicated.