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Promoted regeneration of injured spinal cord by acellular humoral factors, aiming at clinical applications

Research Project

Project/Area Number 16K11390
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Plastic surgery
Research InstitutionAino University

Principal Investigator

Ide Chizuka  藍野大学, 医療保健学部, 教授 (70010080)

Co-Investigator(Kenkyū-buntansha) 兼清 健志  藍野大学, 中央研究施設, 講師 (20525399)
中野 法彦  藍野大学, 中央研究施設, 准教授 (40322721)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords脊髄損傷 / 液性有効因子 / 骨髄間質細胞 / 培養上清 / 歩行運動 / 再生軸索 / 免疫組織化学 / 電子顕微鏡 / コラーゲンマトリックス / BBB / 歩行機能 / 髄液内投与 / 栄養因子 / 神経再生 / 有効因子分画 / 内在的再生能 / 再生医学 / 液性因子
Outline of Final Research Achievements

Neuregulin2 released from astrocytes promoted the survival and neurite extension of rat hippocampus-derived neurons in vitro. The injection of the supernatant of cultured rat bone marrow stromal cells through the cerebrospinal fluid markedly improved locomotive behaviors of spinal cord injured (SCI) rats, and, at the same time, promoted tissue-repairing, including axonal outgrowth, at the epicenter of the spinal cord lesion. This indicated that the humoral factors released from bone marrow stromal cells have a crucial role in promoting behavioral activities of SCI rats, and facilitated histological repairing of the spinal cord lesion of SCI rats. In addition, multiple transplantations of non-cultured mononuclear cells obtained from the rat bone marrow were efficient in locomotor improvement and tissue repair of SCI rats. These findings indicated that humoral factors released from the bone marrow stromal cells have a crucial role in regeneration of injured spinal cord.

Academic Significance and Societal Importance of the Research Achievements

従来、脊髄損傷の治療には、細胞移植が主流である。移植細胞は脊髄組織内に組み込まれて再生軸索の伸長やグリア細胞の再生などを促進して、脊髄損傷の治療をもたらすというのが基本的な概念である。しかし実際には、移植細胞は2-3週後に消失するにも拘らず、再生軸索は伸び、機能的改善も見られる。これは移植細胞から分泌される液性有効因子の効果と考えられる。有効因子の本体は不明だが、培養上清が強い効果を持っていることから、培養上清に含まれる複数の因子が複合的に作用していると考えられる。液性有効因子は髄液経由の投与で、患者に苦痛を与える事なく複数回の投与が可能であるので、臨床的には有利な方法である。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (25 results)

All 2019 2018 2017 2016

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (16 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Structures of filum terminale and characteristics of ependymal cells of its central canal in rats2019

    • Author(s)
      Nakano Norihiko、Kanekiyo Kenji、Yamada Yoshihiro、Tamachi Masahiro、Suzuki Yoshihisa、Fukushima Masatoshi、Saito Fukuki、Abe Seiya、Tsukagoshi Chihiro、Miyamoto Chimi、Ide Chizuka
    • Journal Title

      Brain Research

      Volume: 1707 Pages: 208-215

    • DOI

      10.1016/j.brainres.2018.11.038

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of intrathecal injection of the conditioned medium of bone marrow stromal cells on the spinal cord injury of rats.2018

    • Author(s)
      Kanekiyo K, Homma T, Nakano N, Yamada Y, Tamachi M, Suzuki Y, Fukushima M, Saito F, Ide C.
    • Journal Title

      Journal of Neurotrauma

      Volume: 35 Issue: 3 Pages: 521-532

    • DOI

      10.1089/neu.2017.5201

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Effects of multiple-injection of bone marrow mononuclear cells on spinal cord injury of rats.2017

    • Author(s)
      Kanekiyo K, Nakano N, Homma T, Yamada Y, Tamachi M, Suzuki Y, Fukushima M, Saito F, Ide C.
    • Journal Title

      J Neurotrauma

      Volume: 1 Issue: 21 Pages: 3003-3011

    • DOI

      10.1089/neu.2016.4841

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 骨髄間質細胞由来因子による神経再生2017

    • Author(s)
      中野法彦、兼清健志、井出千束
    • Journal Title

      BIO Clinica

      Volume: 32(10) Pages: 82-86

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cell transplantation for the treatment of spinal cord injury -bone marrow stromal cells and choroid plexus epithelial cells.2016

    • Author(s)
      Ide C, Nakano N, Kanekiyo K.
    • Journal Title

      Neural Regeneration Research

      Volume: 11 Pages: 1385-1388

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] NTAK/Neuregulin-2 secreted by astrocytes promotes survival and neurite outgrowth via ErbB3.2016

    • Author(s)
      Nakano N, Kanekiyo K, Nakagawa T, Asahi M, and Ide C.
    • Journal Title

      Neuroscience Letters.

      Volume: 622 Pages: 88-94

    • DOI

      10.1016/j.neulet.2016.04.050

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transplantation of choroid plexus epithelial cells into contusion-injured spinal cord of rats.2016

    • Author(s)
      Kanekiyo K, Nakano N, Noda T, Yamada Y, Suzuki Y, Ohta M, Yokota A, Fukushima M, Ide C.
    • Journal Title

      Restorative Neurology and Neuroscience

      Volume: 34 Pages: 347-366

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The characteristics and functions of NTAK/Neuregulin-2.2016

    • Author(s)
      Nakano N, Ide C., Kanekiyo K
    • Journal Title

      Aino Journal

      Volume: 15

    • Related Report
      2016 Research-status Report
  • [Journal Article] Locomotor improvement of spinal cord-injured rats through body weight support treadmill training by plantar placement of hind paws on the floor.2016

    • Author(s)
      Hayashibe M, Homma T, Fujimoto K, Oi T, Yagi N, Kashihara M, NIshikawa N, Ishizumi Y, Abe S, Hashimoto H, Kanekiyo K, Ide C, Morioka S.
    • Journal Title

      Spinal Cord

      Volume: 54 Pages: 521-529

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Effects of conditioned medium from bone marrow stromal cells on rat spinal cord injury2018

    • Author(s)
      Kanekiyo K, Nakano N, Abe S, Tsukagoshi S, Miyamoto C, Ide C
    • Organizer
      第41回日本神経科学大会,
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脊髄損傷モデルラットに対する骨髄間質細胞培養上清の脳室内投与の効果,2018

    • Author(s)
      兼清健志, 中野法彦, 安部征哉, 塚越千尋, 宮本陳敏, 井出千束
    • Organizer
      第17回日本再生医療学会総会,
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脊髄損傷モデルラットに対する骨髄間質細胞培養上清の効果2018

    • Author(s)
      兼清健志, 中野法彦, 安部征哉, 塚越千尋, 宮本陳敏, 井出千束,
    • Organizer
      第123回日本解剖学会総会・全国学術集会,
    • Related Report
      2018 Annual Research Report
  • [Presentation] Analysis of neuronal cells induced by low adhesive scaffold collagen、2018

    • Author(s)
      Nakano N, Kanekiyo K, Kunii S, Morimoto K, Omae K, Ide C
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 細胞低接着性コラーゲンを足場とした神経系細胞、2018

    • Author(s)
      中野法彦、兼清健志、國井沙織、森本康一、尾前薫、井出千束
    • Organizer
      第59回組織細胞化学会総会・学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脊髄損傷モデルラットに対する骨髄間質細胞培養上清の脳室内投与の効果2018

    • Author(s)
      兼清健志、中野法彦、安部征哉、塚越千尋、宮本陳敏、井出千束
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 脊髄損傷モデルラットに対する骨髄由来単核細胞の複数回移植効果2017

    • Author(s)
      兼清健志、中野法彦、鈴木義久、井出千束
    • Organizer
      第122回日本解剖学会総会・全国学術集会
    • Place of Presentation
      長崎大学坂本キャンパス
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] 骨髄由来単核細胞の脊髄損傷モデルラットへの複数回移植効果の検討2017

    • Author(s)
      兼清健志、中野法彦、鈴木義久、井出千束
    • Organizer
      第16回日本再生医療学会総会、
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
  • [Presentation] NTAK/neuregulin-2 secreted by astrocytes promotes survival and neurite outgrowth of neurons via ErbB32017

    • Author(s)
      Nakano N, Kanekiyo K, Nakagawa T, Asahi M, and Ide C
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Effects of multiple-injection of bone marrow-derived mononuclear cells on spinal cord injury of rats2017

    • Author(s)
      Kanekiyo K, Nakano N, Suzuki Y, and Ide C
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Analysis of astrocytes with brain specific branched O-mannosyl glycans in demyelination2017

    • Author(s)
      Kanekiyo K, Nakano N, and Ide C
    • Organizer
      Consortium of Biological Sciences
    • Related Report
      2017 Research-status Report
  • [Presentation] Therapeutic effect of multiple-injection of bone marrow-derived mononuclear cells on rat spinal cord injury2017

    • Author(s)
      Kanekiyo K, Nakano N, and Ide C
    • Organizer
      Consortium of Biological Sciences
    • Related Report
      2017 Research-status Report
  • [Presentation] アストロサイト由来のNTAK/Neuregulin-2のニューロンに対する作用、2016

    • Author(s)
      中野法彦、兼清健志、中川孝俊、朝日通雄、井出千束
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] Cell transplantation for the treatment of spinal cord injury-bone marrow stromal cells and choroid plexus epithelial cells.2016

    • Author(s)
      Ide C, Kanekiyo K, Nakano N.
    • Organizer
      2016 International Neural Regeneration Symposium & 10th Asia Pacific Symposium on Neural Regeneration
    • Place of Presentation
      Yinchuan, China
    • Year and Date
      2016-07-29
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Cell transplantation for the treatment of spinal cord injury.2016

    • Author(s)
      Kanekiyo K, Nakano N, Ide C.
    • Organizer
      2016 International Neural Regeneration Symposium & 10th Asia Pacific Symposium on Neural Regeneration
    • Place of Presentation
      Yinchuan, China
    • Year and Date
      2016-07-29
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Transplantation of choroid plexus epithelial cells promotes axon regeneration in spinal cord injury.2016

    • Author(s)
      Kanekiyo K, Nakano N, Noda T, Ide C.
    • Organizer
      第39回に本神経科学大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-07-20
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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