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Establishment of regenerative therapy for dogs using delivery system of hepatocyte growth factor secreted from novel canine mesenchymal stem cells

Research Project

Project/Area Number 16H05037
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Veterinary medical science
Research InstitutionThe University of Tokyo

Principal Investigator

Nishimura Ryohei  東京大学, 大学院農学生命科学研究科(農学部), 教授 (80172708)

Co-Investigator(Kenkyū-buntansha) 藤田 直己  東京大学, 大学院農学生命科学研究科(農学部), 特任助教 (10554488)
Research Collaborator Itaka Keiji  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2016: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Keywords犬 / 脊髄再生医療 / 間葉系幹細胞 / 脊髄損傷 / 再生医療 / 肝細胞成長因子 / 静脈投与 / 生体内イメージング / 骨髄間葉系幹細胞 / In vivo イメージング
Outline of Final Research Achievements

We developed stem cell therapy for canine spinal cord injury using a novel mesenchymal stem cell named bone marrow peri-adipocyte cell (BM-PAC). BM-PAC possesses secretion ability of various humoral factors which shows therapeutic effects on spinal cord injury. When BM-PACs were intravenously administrated to a nude mouse spinal cord injury model in acute or sub-acute phase, cells migrated into the lesion and secreted hepatocyte growth factor (HGF) and vascular endothelial growth factor in acute and sub-acute phase, respectively. Through the supply of these factors to the lesion site, BM-PACs protected spinal cord and suppress the progress of damage. Regeneration of spinal cord tissue including axons and myelins could also occur and these histological modification could contribute to the functional recovery. It is expected to apply BM-PAC based-stem cell therapy for dogs with acute and sub-acute spinal cord injury.

Academic Significance and Societal Importance of the Research Achievements

犬では脊髄損傷が多く、重症例では術後の歩行回復が十分ではなく、動物のみならず飼主のQOLも著しく低下する。近年、これらの症例に対するMSCを用いた脊髄再生医療が導入されるようになっているが、科科学的根拠に不足し、MSC移植の効果に期待した盲目的な投与が多くなっている。本研究は、独自に見出した新規MSCであるBM-PACを用い、脊髄再生医療に利用できる性質を有していること、また、動物モデルを用いた有効性・安全性試験を通し、移植法の妥当性、運動機能回復効果が得られるメカニズムについて明らかにし、科学的根拠に基づいた犬の脊髄再生医療を開発に貢献した。

Report

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

    (23 results)

All 2019 2018 2017 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (19 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results) Remarks (2 results)

  • [Journal Article] Effect of fibroblast growth factor-2 and serum on canine mesenchymal stem cell chondrogenesis2018

    • Author(s)
      Endo Kentaro、Fujita Naoki、Nakagawa Takayuki、Nishimura Ryohei
    • Journal Title

      Tissue Engineering Part A

      Volume: 印刷中 Issue: 11-12 Pages: 901-910

    • DOI

      10.1089/ten.tea.2018.0177

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isolation and Characterization of Multipotent Mesenchymal Stem Cells Adhering to Adipocytes in Canine Bone Marrow2017

    • Author(s)
      Lin Hsing-Yi, Fujita Naoki, Endo Kentaro, Morita Maresuke, Takeda Tae, Nakagawa Takayuki, and Nishimura Ryohei
    • Journal Title

      Stem Cells and Development

      Volume: 26 Issue: 6 Pages: 431-440

    • DOI

      10.1089/scd.2016.0200

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 犬の新規骨髄間葉系幹細胞(BM-PACs)の神経細胞分化誘導2019

    • Author(s)
      羽生航、藤田直己、陳君妍、武田妙、遠藤建太郎、中川貴之、西村亮平
    • Organizer
      第18回日本再生医療学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 犬間葉系幹細胞のHoming機能と血管新生効果に着目した脊髄損傷に対する移植療法の開発2019

    • Author(s)
      武田妙、藤田直己、羽生航、陳君妍、遠藤健太郎、中川貴之、西村亮平
    • Organizer
      第18回日本再生医療学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 急性期脊髄損傷モデルを用いた犬間葉系幹細胞の経静脈移植効果の検討2019

    • Author(s)
      陳君妍、藤田直己、羽生航、武田妙、遠藤健太郎、中川貴之、西村亮平
    • Organizer
      第18回日本再生医療学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] バイオ3Dプリンタを用いた犬間葉系幹細胞からの軟骨組織構築における低酸素環境の影響2019

    • Author(s)
      遠藤健太郎、藤田直己、國富芳博、高井治美、鳥井蓉子、武田妙、陳君研、羽生航、中川貴之、西村亮平
    • Organizer
      第18回日本再生医療学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] FGF-2 enhances multipotency of canine mesenchymal stem cells through maintenance of undifferentiated state2018

    • Author(s)
      W. Hanyu, N. Fujita, J. Chen, T. Takeda, K. Endo,T. Nakagawa, R. Nishimura
    • Organizer
      8th Annual Congress of Asian Society of Veterinary Surgery
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Homing ability and angiogenesis effect of canine mesenchymal stem cell has therapeutic effect on sub-acute spinal cord injury2018

    • Author(s)
      Tae Takeda, Junjien Chen, Kentaro Endo, Wataru Hanyu, Naoki Fujita, Takayuki Nakagawa, Ryohei Nishimura
    • Organizer
      8th Annual Congress of Asian Society of Veterinary Surgery
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Intravenous transplantation of Canine mesenchymal stem cells for mice acute spinal cord2018

    • Author(s)
      J. Chen, N. Fujita, T. Takeda, K. Endo, W. Hanyu, T. Nakagawa, R. Nishimura
    • Organizer
      8th Annual Congress of Asian Society of Veterinary Surgery
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 塩基性線維芽細胞増殖因子が犬間葉系幹細胞の未分化性の維持・獲得に与える影響2018

    • Author(s)
      大田拓也、遠藤健太郎、武田妙、陳君妍、羽生航、藤田直己、中川貴之、西村亮平
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 低酸素環境による犬間葉系幹細胞の硝子軟骨への分化運命決定2018

    • Author(s)
      遠藤健太郎、藤田直己、武田妙、陳君妍、羽生航、中川貴之、西村亮平
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 亜急性期脊髄損傷に対し経静脈移植した犬間葉系幹細胞の走化性と移植効果2018

    • Author(s)
      武田妙、藤田直己、陳君妍、遠藤健太郎、羽生航、中川貴之、西村亮平
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Challenges to develop stem cell therapy in dogs using novel mesenchymal stem cells isolated from bone marrow.2018

    • Author(s)
      Naoki Fujita
    • Organizer
      TERMIS WC 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 低酸素環境が犬間葉系幹細胞の軟骨分化に与える影響2018

    • Author(s)
      遠藤健太郎、藤田直己、武田妙、陳君妍、中川貴之、西村亮平
    • Organizer
      第17回日本再生医療学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 犬の骨髄脂肪細胞周囲細胞の肝細胞成長因子分泌能と脊髄損傷に対する経静脈移移植の効果2018

    • Author(s)
      武田妙、陳君妍、藤田直己、遠藤健太郎、中川貴之、西村亮平
    • Organizer
      第17回日本再生医療学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 犬の骨髄から分離・培養した新規間葉系幹細胞BM-PACsの性状と再生医療への応用2018

    • Author(s)
      藤田直己
    • Organizer
      第17回日本再生医療学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Transplantation of canine bone marrow peri-adipocyte cells for acute spinal cord injury in mice.2017

    • Author(s)
      林杏怡、藤田直己、遠藤健太郎、中川貴之、西村亮平
    • Organizer
      第16回日本再生医療学会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] 3D Bioprinting of Cartilage Tissue Using Canine Mesenchymal Stem Cell Spheroids under the Optimal Growth Factor Condition2017

    • Author(s)
      Kentaro Endo, Naoki Fujita, Yoshihiro Kunitomi, Tae Takeda, Junyan Chen, Koichi Nakayama,Ryohei Nishimura
    • Organizer
      TERMIS Americas 2017 Annual Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 急性期脊髄損傷に対する犬新規間葉系幹細胞移植の治療効果2017

    • Author(s)
      藤田直己、林杏怡、遠藤健太郎、武田妙、陳君妍、中川貴之、西村亮平
    • Organizer
      第160回日本獣医学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 犬間葉系幹細胞の効率的な軟骨分化条件の検討2017

    • Author(s)
      遠藤健太郎, 藤田直己, 林杏怡、中川貴之, 西村亮平
    • Organizer
      第16回日本再生医療学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Transplantation of canine bone marrow peri-adipocyte cells for acute spinal cord injury in mice2017

    • Author(s)
      HXING-YI LIN, NAOKI FUJITA, KENTARO ENDO, TAKAYUKI NAKAGAWA, RYOHEI NISHIMURA
    • Organizer
      第16回日本再生医療学会
    • Related Report
      2017 Annual Research Report
  • [Remarks] 東京大学獣医外科学研究室HP

    • URL

      http://www.vm.a.u-tokyo.ac.jp/geka/

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
  • [Remarks] 東京大学獣医外科学教室HP

    • URL

      http://www.vm.a.u-tokyo.ac.jp/geka/

    • Related Report
      2016 Annual Research Report

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

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