Human neural stem cells induce functional myelination in mice with severe dysmyelination

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 Matsumoto, Lawrence (Larry) Sherman, Christopher (Chris) Kroenke, Stephen Back

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Abstract

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.

Original languageEnglish (US)
Article number155ra136
JournalScience Translational Medicine
Volume4
Issue number155
DOIs
StatePublished - Oct 10 2012

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Neural Stem Cells
Central Nervous System
Oligodendroglia
Myelin Sheath
Anisotropy
Ataxia
Axons
Transplantation
Magnetic Resonance Imaging
Brain

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Human neural stem cells induce functional myelination in mice with severe dysmyelination. / Uchida, Nobuko; Chen, Kevin; Dohse, Monika; Hansen, Kelly D.; Dean, Justin; Buser, Joshua R.; Riddle, Art; Beardsley, Douglas J.; Wan, Ying; Gong, Xi; Nguyen, Thuan; Cummings, Brian J.; Anderson, Aileen J.; Tamaki, Stanley J.; Tsukamoto, Ann; Weissman, Irving L.; Matsumoto, Steven; Sherman, Lawrence (Larry); Kroenke, Christopher (Chris); Back, Stephen.

In: Science Translational Medicine, Vol. 4, No. 155, 155ra136, 10.10.2012.

Research output: Contribution to journalArticle

Uchida, N, Chen, K, Dohse, M, Hansen, KD, Dean, J, Buser, JR, Riddle, A, Beardsley, DJ, Wan, Y, Gong, X, Nguyen, T, Cummings, BJ, Anderson, AJ, Tamaki, SJ, Tsukamoto, A, Weissman, IL, Matsumoto, S, Sherman, LL, Kroenke, CC & Back, S 2012, 'Human neural stem cells induce functional myelination in mice with severe dysmyelination', Science Translational Medicine, vol. 4, no. 155, 155ra136. https://doi.org/10.1126/scitranslmed.3004371
Uchida, Nobuko ; Chen, Kevin ; Dohse, Monika ; Hansen, Kelly D. ; Dean, Justin ; Buser, Joshua R. ; Riddle, Art ; Beardsley, Douglas J. ; Wan, Ying ; Gong, Xi ; Nguyen, Thuan ; Cummings, Brian J. ; Anderson, Aileen J. ; Tamaki, Stanley J. ; Tsukamoto, Ann ; Weissman, Irving L. ; Matsumoto, Steven ; Sherman, Lawrence (Larry) ; Kroenke, Christopher (Chris) ; Back, Stephen. / Human neural stem cells induce functional myelination in mice with severe dysmyelination. In: Science Translational Medicine. 2012 ; Vol. 4, No. 155.
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