Significance of Remyelination by Neural Stem/Progenitor Cells Transplanted into the Injured Spinal Cord§

Authors

  • Akimasa Yasuda,

    1. Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan
    2. Department of Physiology, Keio University School of Medicine, Tokyo, Japan
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  • Osahiko Tsuji,

    1. Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan
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  • Shinsuke Shibata,

    1. Department of Physiology, Keio University School of Medicine, Tokyo, Japan
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  • Satoshi Nori,

    1. Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan
    2. Department of Physiology, Keio University School of Medicine, Tokyo, Japan
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  • Morito Takano,

    1. Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan
    2. Department of Physiology, Keio University School of Medicine, Tokyo, Japan
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  • Yoshiomi Kobayashi,

    1. Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan
    2. Department of Physiology, Keio University School of Medicine, Tokyo, Japan
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  • Yuichiro Takahashi,

    1. Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan
    2. Department of Physiology, Keio University School of Medicine, Tokyo, Japan
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  • Kanehiro Fujiyoshi,

    1. Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan
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  • Chikako Miyauchi Hara,

    1. Department of Physiology, Keio University School of Medicine, Tokyo, Japan
    2. Laboratory for Cell Function and Dynamics, Advanced Technology Development Group, Brain Science Institute, RIKEN, Saitama, Japan
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  • Atsuhi Miyawaki,

    1. Laboratory for Cell Function and Dynamics, Advanced Technology Development Group, Brain Science Institute, RIKEN, Saitama, Japan
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  • Hirotaka James Okano,

    1. Department of Physiology, Keio University School of Medicine, Tokyo, Japan
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  • Yoshiaki Toyama,

    1. Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan
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  • Masaya Nakamura,

    Corresponding author
    1. Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan
    • Department of Orthopedic surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan
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    • Telephone: +81-3-3353-1211; Fax: +81-3353-6597

  • Hideyuki Okano

    Corresponding author
    1. RIKEN-Keio University Joint Research Laboratory, Brain Science Institute, RIKEN, Saitama, Japan
    2. Department of Physiology, Keio University School of Medicine, Tokyo, Japan
    • Department of Physiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan
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    • Telephone: +81-3-5363-3747; Fax: +81-3-3357-5445


  • Author contributions: A.Y.: conception and design, experiments, data analysis and interpretation, manuscript writing, and final approval of manuscript; O.T.: conception and design, experiments, surgery, and data analysis and interpretation, S.S.: experiments and data analysis and interpretation, S.N.: experiments, surgery, and data interpretation; M.T.: experiments, surgery, and data analysis; Y.K. and Y.T.: experiments and data interpretation; K.F., C.M.H., A.M., H.J.O. and Y.T.: data analysis and interpretation; M.N. and H.O.: conception and design, data analysis and interpretation, manuscript writing, and final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS October 25, 2011.

Abstract

Previous reports of functional recovery from spinal cord injury (SCI) in rodents and monkeys after the delayed transplantation of neural stem/progenitor cells (NS/PCs) have raised hopes that stem cell therapy could be used to treat SCI in humans. More research is needed, however, to understand the mechanism of functional recovery. Oligodendrocytes derived from grafted NS/PCs remyelinate spared axons in the injured spinal cord. Here, we studied the extent of this remyelination's contribution to functional recovery following contusive SCI in mice. To isolate the effect of remyelination from other possible regenerative benefits of the grafted cells, NS/PCs obtained from myelin-deficient shiverer mutant mice (shi-NS/PCs) were used in this work alongside wild-type NS/PCs (wt-NS/PCs). shi-NS/PCs behaved like wt-NS/PCs in vitro and in vivo, with the exception of their myelinating potential. shi-NS/PC-derived oligodendrocytes did not express myelin basic protein in vitro and formed much thinner myelin sheaths in vivo compared with wt-NS/PC-derived oligodendrocytes. The transplantation of shi-NS/PCs promoted some locomotor and electrophysiological functional recovery but significantly less than that afforded by wt-NS/PCs. These findings establish the biological importance of remyelination by graft-derived cells for functional recovery after the transplantation of NS/PCs into the injured spinal cord. STEM CELLS 2011;29:1983–1994.

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