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Neuroprotection and Regeneration of the Spinal Cord pp 147–167Cite as

Recombinant Human Hepatocyte Growth Factor Promotes Functional Recovery After Spinal Cord Injury

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Abstract

Hepatocyte growth factor (HGF), which is a potent mitogen for mature hepatocytes and a mediator of the inflammatory responses to tissue injury, was recently highlighted as a potent neurotrophic factor in the central nervous system. We revealed that introducing exogenous HGF into the injured rat spinal cord using a herpes simplex virus-1 vector significantly reduces the area of damaged tissue and promotes functional recovery. However, this rat study did not examine the therapeutic effects of administering HGF after injury, which is the most critical issue for clinical application. To translate this strategy to human treatment, we induced a contusive cervical SCI in the common marmoset, a primate, and then administered recombinant human HGF (rhHGF) intrathecally. Motor function was assessed using an original open-field scoring system focusing on manual function, including reach-and-grasp performance and hand placement in walking. The intrathecal rhHGF preserved the corticospinal fibers and myelinated areas, thereby promoting functional recovery. This study demonstrates the therapeutic effects, safety, and clinical efficacy of intrathecal rhHGF treatment for SCI in adult nonhuman primates and the possibility that this novel therapy may be suitable for clinical application.

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Acknowledgements

 This work was supported by grants from Grants-in-Aid for Scientific Research from JSPS and the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT), the Project for Realization of Regenerative Medicine and Support for the Core Institutes for iPS Cell Research from MEXT, and by a grant-in-aid for the Global COE program from MEXT to Keio University. Research on Measures for Intractable Diseases from the Japanese Ministry of Health Labor and Welfare of Japan, and by “Super Special Consortia” for Supporting the Development of Cutting-edge Medical Care. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflict of Interest  Dr. Toshikazu Nakamura had reported that he was employed by Osaka University as a professor of Kringle Pharma Joint Research Division for Regenerative Drug Discovery in Osaka University, which is sponsored by Kringle Pharma, Inc. (KP), Osaka, Japan. rhHGF protein used in this study was kindly provided by KP. Dr. Funakoshi has served as a scientific advisor of KP. The other authors have declared that no competing interests exist.

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Shinjuku-ku, 160-8582, Japan

    Kazuya Kitamura, Akio Iwanami, Kanehiro Fujiyoshi, Jun-ichi Yamane, Yoshiaki Toyama & Masaya Nakamura

  2. Department of Orthopedic Surgery, Hiratsuka City Hospital, Hiratsuka, Kanagawa, 254-0065, Japan

    Kazuya Kitamura

  3. Department of Physiology, Keio University School of Medicine, Tokyo, Shinjuku-ku, 160-8582, Japan

    Keigo Hikishima & Hideyuki Okano

  4. Central Institute for Experimental Animals, Tonomachi, Kawasaki, Kanagawa, 210-0821, Japan

    Keigo Hikishima

  5. Center for Advanced Research and Education, Asahikawa Medical University, Midorigaoka, Asahikawa, Hokkaido, 078-8510, Japan

    Hiroshi Funakoshi

  6. Kringle Pharma Joint Research Division for Regenerative Drug Discovery, Center for Advanced Science and Innovation, Osaka University, Osaka, 565-0871, Japan

    Toshikazu Nakamura

  7. Department of Neurology, Tohoku University School of Medicine, Sendai, Miyagi, 980-8574, Japan

    Masashi Aoki

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  1. Kazuya Kitamura
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Correspondence to Masaya Nakamura .

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Editors and Affiliations

  1. Dept of Orthop & Rehabilit Med, University of Fukui Faculty of Medical Sciences, Yoshida-gun, Fukui, Japan

    Kenzo Uchida

  2. Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Tokyo, Japan

    Masaya Nakamura

  3. Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

    Hiroshi Ozawa

  4. Department of Orthopedic Surgery, Faculty of Medicine The University of Tokushima, Tokushima, Tokushima, Japan

    Shinsuke Katoh

  5. Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Tokyo, Japan

    Yoshiaki Toyama

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Kitamura, K. et al. (2014). Recombinant Human Hepatocyte Growth Factor Promotes Functional Recovery After Spinal Cord Injury. In: Uchida, K., Nakamura, M., Ozawa, H., Katoh, S., Toyama, Y. (eds) Neuroprotection and Regeneration of the Spinal Cord. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54502-6_14

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  • DOI: https://doi.org/10.1007/978-4-431-54502-6_14

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