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

Item Type:	Article
Title:	Cell surface glycan engineering of neural stem cells augments neurotropism and improves recovery in a murine model of multiple sclerosis
Creators Name:	Merzaban, J.S. and Imitola, J. and Starossom, S.C. and Zhu, B. and Wang, Y. and Lee, J. and Ali, A.J. and Olah, M. and Abuelela, A.F. and Khoury, S.J. and Sackstein, R.
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.
Keywords:	Exofucosylation, Glycan Engineering, HCELL, Multiple Sclerosis, Neural Stem Cell, Animals, Mice
Source:	Glycobiology
ISSN:	0959-6658
Publisher:	Oxford University Press
Volume:	25
Number:	12
Page Range:	1392–1409
Date:	December 2015
Additional Information:	Copyright © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Official Publication:	https://doi.org/10.1093/glycob/cwv046
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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