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Development of induced Drug-Cells for treating Arthritis (DCA) using human ES cells for osteoarthritis

Research Project

Project/Area Number 19K22677
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Saito Taku  東京大学, 医学部附属病院, 准教授 (30456107)

Co-Investigator(Kenkyū-buntansha) 河田 学  日本学術振興会, 海外特別研究員 (10803174)
森 大典  東京大学, 医学部附属病院, 届出研究員 (60835354)
Project Period (FY) 2019-06-28 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords変形性膝関節症 / ヒトES細胞 / 細胞製剤の開発 / 分化誘導条件 / 変形性関節症 / 整形外科学 / 細胞製剤
Outline of Research at the Start

変形性関節症は加齢とともに軟骨がすり減り、関節全体が変形して痛みを来す疾患ですが、薬を使っても痛みを抑えることが難しい場合も多くみられます。脂肪などから培養した幹細胞を関節に注射することで痛みが長期間抑えられることが分かってきましたが、この治療法は費用が高くなることが問題となっています。本研究は、培養細胞技術や変形性関節症のモデルマウスも駆使して、ヒト多能性幹細胞から治療効果の高い細胞を分化誘導する方法を開発することを目指します。

Outline of Final Research Achievements

We developed ”induced Drug-Cells for treating Arthritis (DCA)” using human ES cells for osteoarthritis. Previously we reported that human iPS cells toward chondrocytes by two small-molecule compounds (2C protocol). Based on this 2C protocol, we improved the culture system of human ES cells to differentiate chondrocyte.
And then, we analyzed the expression markers after induced chondrocytes from human ES cells by improved 2C protocol and evaluated the effect of DCA on in vivo osteoarthritis mouse model.

Academic Significance and Societal Importance of the Research Achievements

変形性関節症は強い痛みによって中高年のADLを著しく低下させるが、痛みの制御はしばしば困難で現在もその進行を止める術はない。最近は脂肪幹細胞の関節注射が治療の切り札として注目を集めているが、良質の細胞を安定的に供給するには困難が伴う。本研究ではiPS細胞より品質差が少ないES細胞を用いて、まずは滑膜幹細胞の分化誘導を目指し、その治療効果を検証する中でさらに治療効果の高い細胞製剤DCAの開発に挑むが、このスタイルは再生医療での革新的技術開発と平行して、関節の組織幹細胞のルーツにも迫る研究であり、困難に満ちているが成功した時の医療・医学両面での成果は計り知れない。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (28 results)

All 2021 2020 2019 Other

All Journal Article (13 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 13 results,  Open Access: 11 results) Presentation (11 results) (of which Int'l Joint Research: 3 results,  Invited: 5 results) Book (2 results) Remarks (2 results)

  • [Journal Article] TRPV2 is involved in induction of lubricin and suppression of ectopic endochondral ossification in articular joints2021

    • Author(s)
      Nakamoto Hideki、Katanosaka Yuki、Chijimatsu Ryota、Mori Daisuke、Xuan Fengjun、Yano Fumiko、Omata Yasunori、Maenohara Yuji、Murahashi Yasutaka、Kawaguchi Kohei、Yamagami Ryota、Inui Hiroshi、Taketomi Shuji、Taniguchi Yuki、Kanagawa Motoi、Naruse Keiji、Tanaka Sakae、Saito Taku
    • Journal Title

      Arthritis & Rheumatology

      Volume: - Issue: 8 Pages: 1441-1450

    • DOI

      10.1002/art.41684

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Primary culture of mouse adipose and fibrous synovial fibroblasts under normoxic and hypoxic conditions2020

    • Author(s)
      SUGIMOTO Hikaru、MURAHASHI Yasutaka、CHIJIMATSU Ryota、MIWA Satoshi、YANO Fumiko、TANAKA Sakae、SAITO Taku
    • Journal Title

      Biomedical Research

      Volume: 41 Issue: 1 Pages: 43-51

    • DOI

      10.2220/biomedres.41.43

    • NAID

      130007801491

    • ISSN
      0388-6107, 1880-313X
    • Year and Date
      2020-02-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lubricin Contributes to Homeostasis of Articular Cartilage by Modulating Differentiation of Superficial Zone Cells2020

    • Author(s)
      Maenohara Yuji、Chijimatsu Ryota、Tachibana Naohiro、Uehara Kosuke、Xuan Fengjun、Mori Daisuke、Murahashi Yasutaka、Nakamoto Hideki、Oichi Takeshi、Chang Song Ho、Matsumoto Takumi、Omata Yasunori、Yano Fumiko、Tanaka Sakae、Saito Taku
    • Journal Title

      Journal of Bone and Mineral Research

      Volume: 36 Issue: 4 Pages: 792-802

    • DOI

      10.1002/jbmr.4226

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evidence that TD‐198946 enhances the chondrogenic potential of human synovium‐derived stem cells through the NOTCH3 signaling pathway2020

    • Author(s)
      Kobayashi Masato、Chijimatsu Ryota、Hart David A.、Hamamoto Shuichi、Jacob George、Yano Fumiko、Saito Taku、Shimomura Kazunori、Ando Wataru、Chung Ung‐il、Tanaka Sakae、Yoshikawa Hideki、Nakamura Norimasa
    • Journal Title

      Journal of Tissue Engineering and Regenerative Medicine

      Volume: 15 Issue: 2 Pages: 103-115

    • DOI

      10.1002/term.3149

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The small compound, TD-198946, protects against intervertebral degeneration by enhancing glycosaminoglycan synthesis in nucleus pulposus cells2020

    • Author(s)
      Kushioka Junichi、Kaito Takashi、Chijimatsu Ryota、Okada Rintaro、Ishiguro Hiroyuki、Bal Zeynep、Kodama Joe、Yano Fumiko、Saito Taku、Chung Ung-il、Tanaka Sakae、Yoshikawa Hideki
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 14190-14190

    • DOI

      10.1038/s41598-020-71193-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Associations of clinical outcomes and MRI findings in intra-articular administration of autologous adipose-derived stem cells for knee osteoarthritis2020

    • Author(s)
      Higuchi Junya、Yamagami Ryota、Matsumoto Takumi、Terao Tomohiro、Inoue Keita、Tsuji Shinsaku、Maenohara Yuji、Matsuzaki Tokio、Chijimatsu Ryota、Omata Yasunori、Yano Fumiko、Tanaka Sakae、Saito Taku
    • Journal Title

      Regenerative Therapy

      Volume: 14 Pages: 332-340

    • DOI

      10.1016/j.reth.2020.04.003

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Type 2 innate lymphoid cells inhibit the differentiation of osteoclasts and protect from ovariectomy-induced bone loss2020

    • Author(s)
      Omata Yasunori、Frech Michael、Lucas S?bastien、Primbs Tatjana、Knipfer Lisa、Wirtz Stefan、Kadono Yuho、Saito Taku、Tanaka Sakae、Sarter Kerstin、Schett Georg、Zaiss Mario M.
    • Journal Title

      Bone

      Volume: 136 Pages: 115335-115335

    • DOI

      10.1016/j.bone.2020.115335

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ear Cartilage Reconstruction Combining Induced Pluripotent Stem Cell-Derived Cartilage and Three-Dimensional Shape-Memory Scaffold2020

    • Author(s)
      Uto Sakura、Hikita Atsuhiko、Sakamoto Tomoaki、Mori Daisuke、Yano Fumiko、Ohba Shinsuke、Saito Taku、Takato Tsuyoshi、Hoshi Kazuto
    • Journal Title

      Tissue Engineering Part A

      Volume: - Issue: 9-10 Pages: 604-617

    • DOI

      10.1089/ten.tea.2020.0106

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 2-Methacryloyloxyethyl Phosphorylcholine Polymer Coating Inhibits Bacterial Adhesion and Biofilm Formation on a Suture: An In Vitro and In Vivo Study2020

    • Author(s)
      Kaneko Taizo、Saito Taku、Shobuike Takeo、Miyamoto Hiroshi、Matsuda Junpei、Fukazawa Kyoko、Ishihara Kazuhiko、Tanaka Sakae、Moro Toru
    • Journal Title

      BioMed Research International

      Volume: 2020 Issue: 1 Pages: 1-8

    • DOI

      10.1155/2020/5639651

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypoxia-inducible factor-1 alpha maintains mouse articular cartilage through suppression of NF-κB signaling2020

    • Author(s)
      Okada Keita、Mori Daisuke、Makii Yuma、Nakamoto Hideki、Murahashi Yasutaka、Yano Fumiko、Chang Song Ho、Taniguchi Yuki、Kobayashi Hiroshi、Semba Hiroaki、Takeda Norihiko、Piao Wen、Hanaoka Kenjiro、Nagano Tetsuo、Tanaka Sakae、Saito Taku
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 5425-5425

    • DOI

      10.1038/s41598-020-62463-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Stepwise strategy for generating osteoblasts from human pluripotent stem cells under fully defined xeno-free conditions with small-molecule inducers2020

    • Author(s)
      Zujur Denise、Kanke Kosuke、Onodera Shoko、Tani Shoichiro、Lai Jenny、Azuma Toshifumi、Xin Xiaonan、Lichtler Alexander C.、Rowe David W.、Saito Taku、Tanaka Sakae、Masaki Hideki、Nakauchi Hiromitsu、Chung Ung-il、Hojo Hironori、Ohba Shinsuke
    • Journal Title

      Regenerative Therapy

      Volume: 14 Pages: 19-31

    • DOI

      10.1016/j.reth.2019.12.010

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oral administration of EP4-selective agonist KAG-308 suppresses mouse knee osteoarthritis development through reduction of chondrocyte hypertrophy and TNF secretion2019

    • Author(s)
      Murahashi Yasutaka、Yano Fumiko、Chijimatsu Ryota、Nakamoto Hideki、Maenohara Yuji、Amakawa Masahiro、Miyake Yoshihide、Yamanaka Hiroyuki、Iba Kousuke、Yamashita Toshihiko、Tanaka Sakae、Saito Taku
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 20329-20329

    • DOI

      10.1038/s41598-019-56861-6

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Wnt/β-catenin signaling contributes to articular cartilage homeostasis through lubricin induction in the superficial zone2019

    • Author(s)
      Xuan Fengjun、Yano Fumiko、Mori Daisuke、Chijimatsu Ryota、Maenohara Yuji、Nakamoto Hideki、Mori Yoshifumi、Makii Yuma、Oichi Takeshi、Taketo Makoto Mark、Hojo Hironori、Ohba Shinsuke、Chung Ung-il、Tanaka Sakae、Saito Taku
    • Journal Title

      Arthritis Research & Therapy

      Volume: 21 Issue: 1 Pages: 247-247

    • DOI

      10.1186/s13075-019-2041-5

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ADAM17/TACE accerates osteoarthritis develpoment through EGFR signaling and TNF pathways2021

    • Author(s)
      Kaneko T, Yano F, Chijimatsu R, Tanaka S, Saito T
    • Organizer
      2021 Auunal Meeting of the Orthopaedic Resarch Society
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ルブリシンは関節軟骨最表層細胞の分化を抑制し 軟骨のホメオスタシスを維持している2021

    • Author(s)
      前之原 悠司 千々松 良太 中元 秀樹 矢野 文子 齋藤 琢
    • Organizer
      第33回日本軟骨代謝学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Runx3 protects articular cartilage by direct induction of Prg4.2020

    • Author(s)
      Kosei Nagata, Taku Saito, Fumiko Yano, Hirnori Hojo, Yasuhide Iwanaga, and Sakae Tanaka.
    • Organizer
      ASBMR 2020 Annual Meeting
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Notch signaling contributes to articular cartilage homeostasis by suppressing differentiation of superficial zone cells2020

    • Author(s)
      Iwanaga Y, Nagata K, Yano F, Tanaka S, Sai
    • Organizer
      ASBMR 2020 Annual Meeting
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Notchは最表層細胞の維持を介して関節軟骨の恒常性に貢献する2020

    • Author(s)
      岩永康秀、永田向生、千々松良太、矢野文子、田中栄、齋藤琢
    • Organizer
      第35回日本整形外科学会基礎学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Taceは変形性関節症を促進的に制御する2020

    • Author(s)
      金子泰三、千々松良太、矢野文子、堀内圭輔、田中栄、齋藤
    • Organizer
      第38回日本骨代謝学会学術集
    • Related Report
      2020 Annual Research Report
  • [Presentation] OAの病態における軟骨と周囲組織との関連2020

    • Author(s)
      齋藤琢
    • Organizer
      第48回日本関節病学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 関節軟骨層ごとの主要シグナルの役割2020

    • Author(s)
      齋藤琢
    • Organizer
      第35回日本整形外科学会基礎学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 関節軟骨の維持機構2020

    • Author(s)
      齋藤琢
    • Organizer
      第64回日本リウマチ学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 変形性関節症の分子病態と治療法開発2019

    • Author(s)
      齋藤琢
    • Organizer
      第92回日本整形外科学会学術総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 変形性関節症の分子病態と治療法の開発2019

    • Author(s)
      齋藤琢
    • Organizer
      第68回東日本整形災害外科学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Book] 変形性関節症の分子病態と治療法開発2020

    • Author(s)
      齋藤琢
    • Total Pages
      5
    • Publisher
      日本整形外科学会雑誌
    • Related Report
      2020 Annual Research Report
  • [Book] 関節軟骨のメカノバイオロジ2020

    • Author(s)
      齋藤琢
    • Total Pages
      6
    • Publisher
      実験医学
    • Related Report
      2020 Annual Research Report
  • [Remarks] 東京大学医学部附属病院 整形外科

    • URL

      http://www.u-tokyo-ortho.jp/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 東京大学医学部整形外科

    • URL

      http://www.u-tokyo-ortho.jp/

    • Related Report
      2019 Research-status Report

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Published: 2019-07-04   Modified: 2022-05-26  

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