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 G. Matsumoto; Larry S. Sherman; Christopher D. Kroenke; Stephen A. Back

doi:10.1126/scitranslmed.3004371

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 G. Matsumoto, Larry S. Sherman, Christopher D. Kroenke, Stephen A. Back

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107 Scopus citations

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 language	English (US)
Article number	155ra136
Journal	Science translational medicine
Volume	4
Issue number	155
DOIs	https://doi.org/10.1126/scitranslmed.3004371
State	Published - Oct 10 2012

ASJC Scopus subject areas

General Medicine

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Uchida, N., Chen, K., Dohse, M., Hansen, K. D., Dean, J., Buser, J. R., Riddle, A., Beardsley, D. J., Wan, Y., Gong, X., Nguyen, T., Cummings, B. J., Anderson, A. J., Tamaki, S. J., Tsukamoto, A., Weissman, I. L., Matsumoto, S. G., Sherman, L. S., Kroenke, C. D., & Back, S. A. (2012). Human neural stem cells induce functional myelination in mice with severe dysmyelination. Science translational medicine, 4(155), Article 155ra136. https://doi.org/10.1126/scitranslmed.3004371

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, SG , Sherman, LS , Kroenke, CD & Back, SA 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

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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.",

author = "Nobuko Uchida and Kevin Chen and Monika Dohse and Hansen, {Kelly D.} and Justin Dean and Buser, {Joshua R.} and Art Riddle and Beardsley, {Douglas J.} and Ying Wan and Xi Gong and Thuan Nguyen and Cummings, {Brian J.} and Anderson, {Aileen J.} and Tamaki, {Stanley J.} and Ann Tsukamoto and Weissman, {Irving L.} and Matsumoto, {Steven G.} and Sherman, {Larry S.} and Kroenke, {Christopher D.} and Back, {Stephen A.}",

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AU - Uchida, Nobuko

AU - Chen, Kevin

AU - Dohse, Monika

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AU - Riddle, Art

AU - Beardsley, Douglas J.

AU - Wan, Ying

AU - Gong, Xi

AU - Nguyen, Thuan

AU - Cummings, Brian J.

AU - Anderson, Aileen J.

AU - Tamaki, Stanley J.

AU - Tsukamoto, Ann

AU - Weissman, Irving L.

AU - Matsumoto, Steven G.

AU - Sherman, Larry S.

AU - Kroenke, Christopher D.

AU - Back, Stephen A.

PY - 2012/10/10

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N2 - 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.

AB - 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.

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

Abstract

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