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Establishment of regenerative medicine for musculoskeletal system using clinical-grade canine iPS cells

Research Project

Project/Area Number 20H03156
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 42020:Veterinary medical science-related
Research InstitutionNihon University

Principal Investigator

EDAMURA Kazuya  日本大学, 生物資源科学部, 教授 (80366624)

Co-Investigator(Kenkyū-buntansha) 村田 大紀  佐賀大学, 医学部, 助教 (00772683)
塩澤 誠司  久留米大学, 医学部, 准教授 (10447039)
鳩谷 晋吾  大阪公立大学, 生命環境科学研究科, 准教授 (40453138)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000)
Fiscal Year 2022: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords再生医療 / 運動器疾患 / iPS細胞 / 間葉系幹細胞 / 獣医 / 犬
Outline of Research at the Start

本研究の概要は、臨床グレードの犬の人工多能性幹細胞(iPS細胞)を利用して、運動器疾患に対する細胞療法および再生医療の実用化を目指す研究である。まずは、犬のiPS細胞から均一性の高い間葉系幹細胞を作製し、変形性関節症の治療への応用を試みる。次いで、拒絶反応の少ない犬のiPS細胞の備蓄や、ゲノム編集技術を用いて拒絶反応が生じにくいiPS細胞の作製を試みる。最後に、犬のiPS細胞から培養軟骨や培養靱帯を作製する。本研究は、臨床グレードの犬のiPS細胞を用いた治療を具現化して動物の生活の質を著しく改善できるだけでなく、ヒトでの臨床応用に向けたトランスレーショナルリサーチとしても重要な成果が得られる。

Outline of Final Research Achievements

A basic study to realize regenerative therapy for joint disorders using clinical-grade canine induced pluripotent stem (iPS) cells was performed. First, we focused on tissue derived from canine fetal appendages and established a highly efficient method for generating iPS cells by using the umbilical cord. Next, we found the optimal conditions for inducing differentiation of canine umbilical cord-derived iPS cells into mesenchymal stem cells (MSCs). We also confirmed the safety of intra-articular administration of MSCs in dogs. In addition, we were able to induce differentiation into chondrocytes by pellet culture of canine iPS cell-derived MSCs. Furthermore, we partially contributed to the fabrication of articular cartilage and ligament-like tissue from iPS cell-derived MSCs using three-dimensional cell stacking technology with a bio-3D printer.

Academic Significance and Societal Importance of the Research Achievements

本研究は、臨床グレードの犬の人工多能性幹細胞(iPS細胞)を利用して、変形性関節症に対する細胞療法と、関節軟骨および靱帯の再生医療の実用化を目指した極めて実際的な研究である。現在のところ、臨床応用が可能な犬のiPS細胞は研究代表者らの施設でしか保有しておらず、本研究は世界初・日本発の技術として世界的に注目されている。本研究の成果は、犬の運動器疾患に対する効果の高い治療法を具現化し、動物の生活の質を著しく改善させることができるだけでなく、根治の困難であった運動器疾患の新規治療法の開発に大きく貢献することができる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (30 results)

All 2023 2022 2021 2020

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (23 results) (of which Int'l Joint Research: 4 results,  Invited: 11 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Step‐by‐step protocols for non‐viral derivation of transgene‐free induced pluripotent stem cells from somatic fibroblasts of multiple mammalian species2022

    • Author(s)
      Yoshimatsu Sho、Yamazaki Atsushi、Edamura Kazuya、Koushige Yuko、Shibuya Hisashi、Qian Emi、Sato Tsukika、Okahara Junko、Kishi Noriyuki、Noce Toshiaki、Yamaguchi Yoshifumi、Okano Hideyuki
    • Journal Title

      Development, Growth & Differentiation

      Volume: 64 Issue: 6 Pages: 325-341

    • DOI

      10.1111/dgd.12798

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 特集にあたって-獣医療における再生医療-2022

    • Author(s)
      枝村一弥
    • Journal Title

      Veterinary information

      Volume: 35 Pages: 4-9

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Non-viral derivation of a transgene-free induced pluripotent stem cell line from a male beagle dog2021

    • Author(s)
      Yoshimatsu Sho、Edamura Kazuya、Yoshii Yumi、Iguchi Aozora、Kondo Hirotaka、Shibuya Hisashi、Sato Tsukika、Shiozawa Seiji、Okano Hideyuki
    • Journal Title

      Stem Cell Research

      Volume: 53 Pages: 102375-102375

    • DOI

      10.1016/j.scr.2021.102375

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Non-viral Induction of Transgene-free iPSCs from Somatic Fibroblasts of Multiple Mammalian Species.2021

    • Author(s)
      Yoshimatsu S, Nakajima M, Iguchi A, Sanosaka T, Sato T, Nakamura M, Nakajima R, Arai E, Ishikawa M, Imaizumi K, Watanabe H, Okahara J, Noce T, Takeda Y, Sasaki E, Behr R, Edamura K, Shiozawa S, Okano H.
    • Journal Title

      Stem Cell Reports

      Volume: 16 Issue: 4 Pages: 754-770

    • DOI

      10.1016/j.stemcr.2021.03.002

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Generation and validation of a common marmoset embryonic stem cell line ActiCre-B1 that ubiquitously expresses a tamoxifen-inducible Cre-driver2021

    • Author(s)
      Yoshimatsu Sho、Ohtsu Kanae、Sato Tsukika、Yamamoto Masafumi、Sasaki Erika、Shiozawa Seiji、Okano Hideyuki
    • Journal Title

      Stem Cell Research

      Volume: 51 Pages: 102164-102164

    • DOI

      10.1016/j.scr.2021.102164

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Direct Neuronal Reprogramming of Common Marmoset Fibroblasts by ASCL1, microRNA-9/9*, and microRNA-124 Overexpression2020

    • Author(s)
      Nemoto Akisa、Kobayashi Reona、Yoshimatsu Sho、Sato Yuta、Kondo Takahiro、Yoo Andrew S.、Shiozawa Seiji、Okano Hideyuki
    • Journal Title

      Cells

      Volume: 10 Issue: 1 Pages: 6-6

    • DOI

      10.3390/cells10010006

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 獣医学領域における再生医療の現状 何が真実か?2023

    • Author(s)
      枝村一弥
    • Organizer
      第19回日本獣医内科学アカデミー学術大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Overview 獣医再生医療をめぐる最近の動向と今後の展開2023

    • Author(s)
      枝村一弥
    • Organizer
      第22回日本再生医療学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] RNA reprogrammingを用いた犬の人工多能性幹細胞の樹立2023

    • Author(s)
      山﨑敦史,枝村一弥
    • Organizer
      第22回日本再生医療学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 犬の臍帯由来iPS細胞を用いたiPS細胞由来間葉系幹細胞の開発2023

    • Author(s)
      山﨑敦史,枝村一弥
    • Organizer
      第5回獣医幹細胞生物研究会
    • Related Report
      2022 Annual Research Report
  • [Presentation] イヌiPS細胞の作製と今後の課題2023

    • Author(s)
      鳩谷晋吾
    • Organizer
      第22回日本再生医療学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 新たな効率の高い犬の人工多能性幹細胞の樹立法の確立2022

    • Author(s)
      山﨑敦史,立花聖果,枝村一弥
    • Organizer
      第17回日本獣医再生医療学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 臨床応用可能な犬iPS細胞の創生と社会実装2022

    • Author(s)
      枝村一弥
    • Organizer
      動物再生医療推進協議会 勉強会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Tibial plateau levering osteotomy on cruciate ligament tension in dogs2022

    • Author(s)
      Hinano Eto, Kazuya Edamura, Shota Kaneda, Koji Tanegashima, Yuma Tomo, Kei Hayashi
    • Organizer
      31st European College of Veterinary Surgeons Annual Scientific Meeting
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] これからの獣医再生医療の臨床2022

    • Author(s)
      枝村一弥
    • Organizer
      福岡市獣医師会講演会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 獣医学領域における再生医療の現状 何ができるのか? 何が真実か?2022

    • Author(s)
      枝村一弥
    • Organizer
      横浜市獣医師会 講演会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 獣医学領域における再生医療の現状 何ができるのか? 何が真実か?2022

    • Author(s)
      枝村一弥
    • Organizer
      関西地区合同オンラインセミナー
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] イヌiPS細胞の安定的かつ効率的なフィーダーフリー培養条件の検討2022

    • Author(s)
      長倉京哉、塚本雅也、木村和人、杉浦喜久弥、鳩谷晋吾
    • Organizer
      第165回日本獣医学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 犬の臍帯由来人工多能性幹細胞の樹立2022

    • Author(s)
      山﨑敦史,立花聖果,枝村一弥
    • Organizer
      第21回日本再生医療学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 獣医再生医療がヒトの再生医療に貢献できること -One HealthとTranslational medicine-2022

    • Author(s)
      枝村一弥
    • Organizer
      第21回日本再生医療学会総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] ウサギ脂肪由来幹細胞からなるscaffold-free 3次元構造体による膝蓋腱再生2022

    • Author(s)
      宗像季生子, 村田大紀, 藤本亮太, 高尾省子, 三宅美保, 野中俊宏, 永石友公子, 中村アンナ, 中山 功一
    • Organizer
      第21回日本再生医療学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 獣医学領域における再生医療の現状 何ができるのか? 何が真実か2021

    • Author(s)
      枝村一弥
    • Organizer
      湘南臨床研究会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Developing a 3D hiPSC-derived culture model system for inducing endogenous tau aggregation2021

    • Author(s)
      Sumihiro Maeda, Hayato Hiramine , Mitsuru Ishikawa, Ikuko Koya, Ryosuke Nagashima, Seiji Shiozawa, Mari Nakamura, Manabu Itoh, Hideyuki Okano
    • Organizer
      International Society for Stem Cell Research 19th annual meeting
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] hiPSC3D培養モデルを用いた内在性タウタンパク質凝集誘導系の開発2021

    • Author(s)
      平峯勇人, 前田純宏, 石川充, 古家育子, 永島崚甫, 塩澤誠司, 中村真理, 伊藤学, 岡野栄之
    • Organizer
      第40回日本認知症学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] イヌiPS細胞から間葉系幹細胞の誘導の試み2021

    • Author(s)
      塚本雅也, 川端千晶, 木村和人, 杉浦喜久弥, 鳩谷晋吾
    • Organizer
      第164回日本獣医学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Tendon/ligament regeneration using a scaffold-free biofabricated 3D construct of autologous adipose tissue-derived mesenchymal stem cells in rabbits2021

    • Author(s)
      Daiki Murata, Ryota Fujimoto, Shoko Takao, Miho Miyake, Anna Maria Nakamura, Koichi Nakayama
    • Organizer
      The 6th Tissue Engineering and Regenerative Medicine International Society World Congress
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] イヌとネコのiPS細胞2021

    • Author(s)
      鳩谷晋吾
    • Organizer
      第16回日本獣医再生医療学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 臨床グレードの犬のiPS細胞の創生および間葉系幹細胞への分化誘導法の開発2021

    • Author(s)
      山﨑敦史, 上田雄貴, 吉井友見, 井口青空, 塩澤誠司, 枝村一弥
    • Organizer
      第4回獣医幹細胞生物研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Regenerative Medicine in the Field of Veterinary Orthopedic Surgery -Recent Evidence and Future Prospects-2020

    • Author(s)
      Kazuya Edamura
    • Organizer
      10th Asian Society of Veterinary Surgery Conference
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Patent(Industrial Property Rights)] 靭帯・腱用人工組織体、その製造方法及びその用途2023

    • Inventor(s)
      村田大紀、三宅美保
    • Industrial Property Rights Holder
      村田大紀、三宅美保
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2022-035798
    • Filing Date
      2023
    • Related Report
      2022 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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