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Transplantation of human neural stem cells for spinal cord injury in primates

Authors

  • A. Iwanami,

    1. Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan
    2. Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, Japan
    3. Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Kawaguchi, Saitama, Japan
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    • A. Iwanami and S. Kaneko contributed equally to this work.

  • S. Kaneko,

    1. Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan
    2. Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, Japan
    3. Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Kawaguchi, Saitama, Japan
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    • A. Iwanami and S. Kaneko contributed equally to this work.

  • M. Nakamura,

    1. Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, Japan
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  • Y. Kanemura,

    1. Tissue Engineering Research Center (TERC), National Institute of Advanced Industrial Science and Technology (AIST), Amagasaki, Hyogo, Japan
    2. Institute for Clinical Research, Osaka National Hospital, Osaka, Japan
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  • H. Mori,

    1. Tissue Engineering Research Center (TERC), National Institute of Advanced Industrial Science and Technology (AIST), Amagasaki, Hyogo, Japan
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  • S. Kobayashi,

    1. Tissue Engineering Research Center (TERC), National Institute of Advanced Industrial Science and Technology (AIST), Amagasaki, Hyogo, Japan
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  • M. Yamasaki,

    1. Institute for Clinical Research, Osaka National Hospital, Osaka, Japan
    2. Department of Neurosurgery, Osaka National Hospital, Osaka, Japan
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  • S. Momoshima,

    1. Department of Radiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan
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  • H. Ishii,

    1. Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan
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  • K. Ando,

    1. Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan
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  • Y. Tanioka,

    1. Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan
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  • N. Tamaoki,

    1. Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan
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  • T. Nomura,

    1. Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan
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  • Y. Toyama,

    1. Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, Japan
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  • H. Okano

    Corresponding author
    1. Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan
    2. Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Kawaguchi, Saitama, Japan
    • Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan
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Abstract

Recent studies have shown that delayed transplantation of neural stem/progenitor cells (NSPCs) into the injured spinal cord can promote functional recovery in adult rats. Preclinical studies using nonhuman primates, however, are necessary before NSPCs can be used in clinical trials to treat human patients with spinal cord injury (SCI). Cervical contusion SCIs were induced in 10 adult common marmosets using a stereotaxic device. Nine days after injury, in vitro-expanded human NSPCs were transplanted into the spinal cord of five randomly selected animals, and the other sham-operated control animals received culture medium alone. Motor functions were evaluated through measurements of bar grip power and spontaneous motor activity, and temporal changes in the intramedullary signals were monitored by magnetic resonance imaging. Eight weeks after transplantation, all animals were sacrificed. Histologic analysis revealed that the grafted human NSPCs survived and differentiated into neurons, astrocytes, and oligodendrocytes, and that the cavities were smaller than those in sham-operated control animals. The bar grip power and the spontaneous motor activity of the transplanted animals were significantly higher than those of sham-operated control animals. These findings show that NSPC transplantation was effective for SCI in primates and suggest that human NSPC transplantation could be a feasible treatment for human SCI. © 2005 Wiley-Liss, Inc.

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