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Intervertebral disc regenerative therapy using bone marrow aspirate concentrate combined with in situ forming bioresorbable ultra-purified alginate gel

Research Project

Project/Area Number 21H03313
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 59020:Sports sciences-related
Research InstitutionHokkaido University

Principal Investigator

Sudo Hideki  北海道大学, 医学研究院, 特任教授 (30374367)

Co-Investigator(Kenkyū-buntansha) 山田 勝久  北海道大学, 大学病院, 助教 (20771893)
岩田 玲  北海道大学, 大学病院, その他 (10374373)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2023: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2022: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2021: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Keywords椎間板再生 / 自家骨髄濃縮液
Outline of Research at the Start

自家骨髄濃縮液(Bone marrow aspirate concentrate、BMAC)は、骨髄液に含まれる間葉系幹細胞などの単核細胞群や液性因子を濃縮して作成される。軟骨損傷や靭帯損傷など筋骨格系領域に対する低侵襲再生医療技術としての有用性が期待されているが、分子メカニズムに立脚した組織修復機序については明らかにされていない。本研究では、全ての競技種目に起こりうるスポーツ障害として広く認知されている椎間板障害に焦点をあて、BMACと椎間板細胞の相互作用による椎間板組織再生メカニズムの分子機序を明らかにするとともに、大型動物による手技の開発を行って臨床応用へと橋渡しする基盤研究とすることを目標とする。

Outline of Final Research Achievements

The regenerative ability of intervertebral discs (IVDs) is restricted due to the poor nutritional supply. We have demonstrated the regenerative effect of implantation of bone marrow aspirate concentrate (BMAC) combined with ultra-purified alginate gel (UPAL gel) for degenerated IVDs in a rabbit model. The purpose of this study is to assess the effectiveness of the implantation of BMAC combined with UPAL gel after discectomy in beagle dogs as a large animal model. Implantation of the BMAC combined with UPAL gel suppresses IVD degeneration after discectomy. In addition, type II collagen positive cells were significantly higher in the BMAC group, suggesting that the implantation of BMAC combined with UPAL gel promoted spontaneous IVD repair. These results support that BMAC combined with UPAL gel implantation after discectomy may be applied in clinical settings as one-step cell-based regenerative therapy for IVD herniation.

Academic Significance and Societal Importance of the Research Achievements

生体内における椎間板の再生能力は著しく低く、椎間板ヘルニアに対するヘルニア摘出術は術後変性を来す要因となる。我々はこれまでに家兎椎間板変性モデルを対象に、アルギン酸を基盤とした高純度硬化性ゲルと骨髄濃縮液(BMAC)の併用による組織再生効果と力学的安定性を示してきた。本研究では、臨床応用を見据えた橋渡し研究としての性能評価試験を行なった。

細胞培養操作を伴う幹細胞移植に比べて一期的処置が可能な本法は、生体侵襲やコスト軽減効果が高く、実臨床における新たな椎間板再生治療法としての有用性は高いと言える。本研究における橋渡し研究の成果が示されたことから今後の臨床への応用が期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (20 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (1 results) Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (8 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Remarks (2 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 2 results)

  • [Int'l Joint Research] Hospital for Special Surgery/Cornell University(米国)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Intervertebral disc degeneration and regeneration: New molecular mechanisms and therapeutics2024

    • Author(s)
      H. Sudo
    • Journal Title

      Cells

      Volume: 13 Issue: 2 Pages: 153-153

    • DOI

      10.3390/cells13020153

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Review: Methodologies to Promote the Differentiation of Mesenchymal Stem Cells for the Regeneration of Intervertebral Disc Cells Following Intervertebral Disc Degeneration2023

    • Author(s)
      Ohnishi Takashi、Homan Kentaro、Fukushima Akira、Ukeba Daisuke、Iwasaki Norimasa、Sudo Hideki
    • Journal Title

      Cells

      Volume: 12 Issue: 17 Pages: 2161-2161

    • DOI

      10.3390/cells12172161

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Injection of Ultra-Purified Stem Cells with Sodium Alginate Reduces Discogenic Pain in a Rat Model2023

    • Author(s)
      Suzuki H, Ura K, Ukeba D, Suyama T, Iwasaki N, Watanabe M, Matsuzaki Y, Yamada K, Sudo H.
    • Journal Title

      Cells

      Volume: 12 Issue: 3 Pages: 505-505

    • DOI

      10.3390/cells12030505

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combination of ultra-purified stem cells with an in situ-forming bioresorbable gel enhances intervertebral disc regeneration2022

    • Author(s)
      Ukeba D, Yamada K, Suyama T, Lebl DR, Tsujimoto T, Nonoyama T, Sugino H, Iwasaki N, Watanabe M, Matsuzaki Y, Sudo H.
    • Journal Title

      EBioMedicine

      Volume: 76 Pages: 103845-103845

    • DOI

      10.1016/j.ebiom.2022.103845

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Causes of and Molecular Targets for the Treatment of Intervertebral Disc Degeneration: A Review.2022

    • Author(s)
      Ohnishi T, Iwasaki N, Sudo H.
    • Journal Title

      Cells

      Volume: 11 Issue: 3 Pages: 394-394

    • DOI

      10.3390/cells11030394

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biomaterials and Cell-Based Regenerative Therapies for Intervertebral Disc Degeneration with a Focus on Biological and Biomechanical Functional Repair: Targeting Treatments for Disc Herniation2022

    • Author(s)
      Yamada K, Iwasaki N, Sudo H.
    • Journal Title

      Cells

      Volume: 11 Issue: 4 Pages: 602-602

    • DOI

      10.3390/cells11040602

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 高純度硬化性アルギン酸ゲルと骨髄濃縮液を併用した椎間板再生治療法の開発2023

    • Author(s)
      筌場大介 石川蓉子 山田勝久 Khin Khin Tha 岩崎倫政 須藤英毅
    • Organizer
      第96回 日本整形外科学会 学術総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Intervertebral disc regenerative therapy using bone marrow aspirate concentrate combined with in situ forming bioresorbable ultra-purified alginate gel2023

    • Author(s)
      Daisuke Ukeba, Yoko Ishikawa, Katsuhisa Yamada, Khin Khin Tha, Norimasa Iwasaki, Hideki Sudo
    • Organizer
      Orthopaedic Research Society
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 生体力学的観点からみた椎間板再生医療への取り組み:超高純度生体吸収性バイオマテリアルと同種骨髄由来間葉系幹細胞を用いた臨床研究2022

    • Author(s)
      須藤 英毅
    • Organizer
      第37回日本整形外科学会基礎学術集会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 超高純度間葉系幹細胞とアルギン酸ナトリウムの椎間板内投与は椎間板性疼痛を軽減する2022

    • Author(s)
      鈴木久崇、浦勝郎、山田勝久、岩崎倫政、伊佐次三津子、渡部正利喜、松崎有未、須藤英毅
    • Organizer
      第37回日本整形外科学会基礎学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 超高純度間葉系幹細胞とアルギン酸ナトリウムの椎間板内投与は椎間板性疼痛を軽減する2022

    • Author(s)
      鈴木久崇、浦勝郎、山田勝久、岩崎倫政、伊佐次三津子、渡部正利喜、松崎有未、須藤英毅
    • Organizer
      第71回東日本整形災害外科学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 3.Commbination of highly-purified mesenchymal stem cells with bioresorbable alginate gel as a regenerative therapy for degenerated intervertebral discs2022

    • Author(s)
      Daisuke Ukeba, Katsuhisa Yamada, Takashi Suyama, Takeru Tsujimoto, Norimasa Iwasaki, Masatoki Watanabe, Yumi Matsuzaki, Hideki Sudo
    • Organizer
      2022 Annual Meeting of Orthopaedic Research Society
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 1.超高純度同種間葉系幹細胞と硬化性ゲルを用いた変性椎間板に対する細胞治療法の開発2021

    • Author(s)
      筌場大介, 陶山隆史, 山田勝久, 辻本武尊, 岩崎倫政, 渡部正利喜, 松崎有未,  須藤英毅
    • Organizer
      第140回北海道整形災害外科学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 2.超高純度同種間葉系幹細胞と硬化性ゲルを用いた変性椎間板に対する細胞治療法の開発2021

    • Author(s)
      須藤英毅, 筌場大介, 陶山隆史, 山田勝久, 辻本武尊, 岩崎倫政, 渡部正利喜, 伊佐次三津子, 松崎有未
    • Organizer
      第36回日本整形外科学会基礎学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Remarks]

    • URL

      https://www.hokudaiseikei.jp/pdf/20230404sudo.pdf

    • Related Report
      2022 Annual Research Report
  • [Remarks] 脊椎・脊髄先端医学分野

    • URL

      https://www.hokudaiseikei.jp/pdf/20210924sudo.pdf

    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] 椎間板再生用組成物2022

    • Inventor(s)
      須藤英毅、他6名
    • Industrial Property Rights Holder
      須藤英毅、他6名
    • Industrial Property Rights Type
      特許
    • Filing Date
      2022
    • Related Report
      2021 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 椎間板再生用組成物2022

    • Inventor(s)
      須藤英毅、他6名
    • Industrial Property Rights Holder
      須藤英毅、他6名
    • Industrial Property Rights Type
      特許
    • Filing Date
      2022
    • Related Report
      2021 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 椎間板再生用組成物2021

    • Inventor(s)
      須藤英毅、他6名
    • Industrial Property Rights Holder
      須藤英毅、他6名
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-167913
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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