Document Detail


Human neural stem cells induce functional myelination in mice with severe dysmyelination.
MedLine Citation:
PMID:  23052293     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Shiverer-immunodeficient (Shi-id) mice demonstrate defective myelination in the central nervous system (CNS) and significant ataxia by 2 to 3 weeks of life. Expanded, banked human neural stem cells (HuCNS-SCs) were transplanted into three sites in the brains of neonatal or juvenile Shi-id mice, which were asymptomatic or showed advanced hypomyelination, respectively. In both groups of mice, HuCNS-SCs engrafted and underwent preferential differentiation into oligodendrocytes. These oligodendrocytes generated compact myelin with normalized nodal organization, ultrastructure, and axon conduction velocities. Myelination was equivalent in neonatal and juvenile mice by quantitative histopathology and high-field ex vivo magnetic resonance imaging, which, through fractional anisotropy, revealed CNS myelination 5 to 7 weeks after HuCNS-SC transplantation. Transplanted HuCNS-SCs generated functional myelin in the CNS, even in animals with severe symptomatic hypomyelination, suggesting that this strategy may be useful for treating dysmyelinating diseases.
Authors:
Nobuko Uchida; Kevin Chen; Monika Dohse; Kelly D Hansen; Justin Dean; Joshua R Buser; Art Riddle; Douglas J Beardsley; Ying Wan; Xi Gong; Thuan Nguyen; Brian J Cummings; Aileen J Anderson; Stanley J Tamaki; Ann Tsukamoto; Irving L Weissman; Steven G Matsumoto; Larry S Sherman; Christopher D Kroenke; Stephen A Back
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science translational medicine     Volume:  4     ISSN:  1946-6242     ISO Abbreviation:  Sci Transl Med     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-11     Completed Date:  2013-03-12     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  101505086     Medline TA:  Sci Transl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  155ra136     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / cytology,  metabolism,  pathology
Central Nervous System / cytology,  metabolism,  pathology
Demyelinating Diseases / therapy*
Humans
Immunohistochemistry
Magnetic Resonance Imaging
Mice
Myelin Sheath / metabolism*
Neural Stem Cells / cytology*,  physiology
Stem Cell Transplantation
Grant Support
ID/Acronym/Agency:
1F30NS066704/NS/NINDS NIH HHS; 1R01NS054044/NS/NINDS NIH HHS; F30 NS066704/NS/NINDS NIH HHS; P51 RR000113/RR/NCRR NIH HHS; P51 RR000163/RR/NCRR NIH HHS; P51RR000163/RR/NCRR NIH HHS; R01 NS054044/NS/NINDS NIH HHS; R37 NS045737/NS/NINDS NIH HHS; R37NS045737-06S1/06S2/NS/NINDS NIH HHS
Comments/Corrections
Erratum In:
Sci Transl Med. 2012 Dec 19;4(165):165er7

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