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Development of cell-based therapy for osteoarthritis using dedifferentiated fat cells

Research Project

Project/Area Number 17H04152
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General internal medicine(including psychosomatic medicine)
Research InstitutionNihon University

Principal Investigator

MATSUMOTO Taro  日本大学, 医学部, 教授 (50366580)

Co-Investigator(Kenkyū-buntansha) 李 ヨキン  日本大学, 医学部, 准教授 (30599048)
風間 智彦  日本大学, 医学部, 助教 (80525668)
中山 渕志  日本大学, 医学部, 助手 (40793401)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2019: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Keywords脂肪細胞 / 変形性膝関節症 / 脱分化脂肪細胞 / 細胞治療 / 間葉系幹細胞 / 再生医学
Outline of Final Research Achievements

Intra-articular injection of mesenchymal stem cells is known to have a therapeutic potential for osteoarthritis (OA) of the knee. Mature adipocyte-derived dedifferentiated fat (DFAT) cells are multipotent cells that have a characteristic similar to mesenchymal stem cells (MSCs). In this study, we investigated the possibility of cell therapy using DFAT cells for OA. We found that DFAT cells expressed several immunomodulatory, anti-inflammatory, and cartilage-related genes in response to inflammatory cytokines. DFAT cells also suppressed the expression of a cartilage matrix-degradation enzyme gene from synovial fibroblasts. We demonstrated that intra-articular injection of DFAT cells inhibit cartilage degeneration in the animal model of OA. Our results indicated the effectiveness of DFAT cell-based therapy for treating OA.

Academic Significance and Societal Importance of the Research Achievements

DFATは少量の脂肪組織から均質なMSC用細胞を大量製造できるユニークな技術である。OA患者からも安定的に調製できるため、既存のMSCなどの治療用細胞に比べ、安全性、コスト面で優位性が高いと考えられる。本研究はOAに対するDFAT細胞治療の有効性と推定される作用機序を初めて明らかにした。OAに対して行われている人工関節置換術は優れた治療法であるが、若年、中年OAでは推奨されず、またその侵襲性の高さから手術に踏み切れない患者も多く存在する。DFATを用いた細胞治療は、このようなOA患者に対する有効な治療戦略となる可能性がある。本研究成果は高齢化社会における健康寿命延伸に寄与するものと考えられる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (22 results)

All 2019 2018 2017 Other

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 6 results) Presentation (10 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Analysis of Cell-To-Cell Interactions between Intervertebral Nucleus Pulposus Cells and Dedifferentiated Fat Cells Using a Coculture System2019

    • Author(s)
      Sakuma Toshiyuki、Matsumoto Taro、Kazama Tomohiko、Tokuhashi Yasuaki
    • Journal Title

      Journal of Nihon University Medical Association

      Volume: 78 Issue: 5 Pages: 285-293

    • DOI

      10.4264/numa.78.5_285

    • NAID

      130007748545

    • ISSN
      0029-0424, 1884-0779
    • Year and Date
      2019-10-01
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of Mature Adipocyte-Derived Dedifferentiated Fat Cells on Formation of Basement Membrane after Cultured Epithelial Autograft on Artificial Dermis2019

    • Author(s)
      Soejima Kazutaka、Kashimura Tsutomu、Kazama Tomohiko、Matsumoto Taro、Nakazawa Hiroaki
    • Journal Title

      Plastic and Reconstructive Surgery

      Volume: 143 Issue: 5 Pages: 983e-992e

    • DOI

      10.1097/prs.0000000000005514

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased Complement 3 With Suppression of miR‐145 Induces the Synthetic Phenotype in Vascular Smooth Muscle Cells From Spontaneously Hypertensive Rats2019

    • Author(s)
      Chen Lan、Fukuda Noboru、Otsuki Tomoyasu、Tanaka Sho、Nakamura Yoshihiro、Kobayashi Hiroki、Matsumoto Taro、Abe Masanori
    • Journal Title

      Journal of the American Heart Association

      Volume: 8 Issue: 10 Pages: 255-262

    • DOI

      10.1161/jaha.119.012327

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of complement 3 in the pathogenesis of hypertension2019

    • Author(s)
      Chen Lan、Fukuda Noboru、Matsumoto Taro、Abe Masanori
    • Journal Title

      Hypertension Research

      Volume: 43 Issue: 4 Pages: 255-262

    • DOI

      10.1038/s41440-019-0371-y

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Construction of 3D Cellular Composites with Stem Cells Derived from Adipose Tissue and Endothelial Cells by Use of Optical Tweezers in a Natural Polymer Solution2019

    • Author(s)
      Yamazaki Takehiro、Kishimoto Toshifumi、Leszczynski Pawel、Sadakane Koichiro、Kenmotsu Takahiro、Watanabe Hirofumi、Kazama Tomohiko、Matsumoto Taro、Yoshikawa Kenichi、Taniguchi Hiroaki
    • Journal Title

      Materials

      Volume: 12 Issue: 11 Pages: 1759-1759

    • DOI

      10.3390/ma12111759

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dedifferentiated fat cells in polyglycolic acid-collagen nerve conduits promote rat facial nerve regeneration2019

    • Author(s)
      Fujimaki Hiroshi、Matsumine Hajime、Osaki Hironobu、Ueta Yoshifumi、Kamei Wataru、Shimizu Mari、Hashimoto Kazuki、Fujii Kaori、Kazama Tomohiko、Matsumoto Taro、Niimi Yosuke、Miyata Mariko、Sakurai Hiroyuki
    • Journal Title

      Regenerative Therapy

      Volume: 11 Pages: 240-248

    • DOI

      10.1016/j.reth.2019.08.004

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a Rat Model of Patulous Eustachian Tube by Mandibular Nerve Resection2019

    • Author(s)
      Harada H, Hirai R, Matsumoto T, Oshima T
    • Journal Title

      Auris Nasus Larynx

      Volume: 印刷中 Issue: 6 Pages: 821-829

    • DOI

      10.1016/j.anl.2019.03.001

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transplantation of dedifferentiated fat cell-derived micromass pellets contributed to cartilage repair in the rat osteochondral defect model.2018

    • Author(s)
      Shimizu Manabu, Matsumoto Taro, Kikuta Shinsuke, Ohtaki Munenori, Kano Koichiro, Taniguchi Hiroaki, Saito Shu, Nagaoka Masahiro, Tokuhashi Yasuaki
    • Journal Title

      Journal of Orthopedic Science

      Volume: 23 Issue: 4 Pages: 688-696

    • DOI

      10.1016/j.jos.2018.03.001

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transplantation of dedifferentiation fat cells promotes intervertebral disc regeneration in a rat intervertebral disc degeneration model2017

    • Author(s)
      Nakayama Enshi、Matsumoto Taro、Kazama Tomohiko、Kano Koichiro、Tokuhashi Yasuaki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 493 Issue: 2 Pages: 1004-1009

    • DOI

      10.1016/j.bbrc.2017.09.101

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 脱分化脂肪細胞を用いた血管再生細胞治療2019

    • Author(s)
      松本太郎
    • Organizer
      第60回日本脈管学会総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ヒト神経芽腫細胞株におけるヒト脱分化脂肪細胞を用いた分化誘導の検討2019

    • Author(s)
      日高綾乃, 土方浩平, 加藤礼保納, 植草省太, 金田英秀, 上原秀一郎, 松本太郎, 越永従道
    • Organizer
      第56回日本小児外科学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ANCA関連腎炎に対する脱分化脂肪細胞(DFAT)治療の開発2019

    • Author(s)
      宇都宮慧,丸山高史, 深澤みゆき, 常見明子, 遠藤守人, 松本太郎, 福田昇, 阿部雅紀
    • Organizer
      第62回日本腎臓学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 糖尿病ラットを用いた脱分化脂肪細胞(DFAT)投与による皮弁生着域拡大効果に関する検討2019

    • Author(s)
      樫村勉, 副島一孝, 菊池雄二, 仲沢弘明, 風間智彦, 松本太郎
    • Organizer
      第11回日本創傷外科学会総会・学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 人工真皮移植時のヒトDFATの血管新生効果-免疫不全マウスによる実験的検討-2019

    • Author(s)
      副島一孝, 樫村勉, 風間智彦, 松本太郎, 仲沢弘明
    • Organizer
      第28回日本形成外科学会基礎学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Enhanced periodontal regeneration by mature adipocyte-derived dedifferentiated fat cells transplantation2019

    • Author(s)
      Akita D, Tsukimura N, Kazama T, Arai Y, Matsumoto T, Honda M
    • Organizer
      4th Meeting of the International Association for Dental Research Asia Pacific Region
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脱分化脂肪細胞による細胞治療の実用化2018

    • Author(s)
      松本太郎
    • Organizer
      第27回日本形成外科学会基礎学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 膝蓋下脂肪体に由来する脱分化脂肪細胞の形質および機能解析2018

    • Author(s)
      谷本浩二, 松本太郎, 長岡悠紀, 風間美奈子, 風間智彦, 山元智衣, 長岡正宏, 斉藤修, 徳橋泰明
    • Organizer
      第33回日本整形外科学会基礎学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ラット椎間板変性モデルに対する脱分化脂肪細胞(DFAT)移植方法による治療効果の検討2018

    • Author(s)
      中山渕志, 小山公行, 風間智彦, 松本太郎, 徳橋泰明
    • Organizer
      第33回日本整形外科学会基礎学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 成熟脂肪細胞の脱分化技術を利用した再生医療2018

    • Author(s)
      松本太郎
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2017 Annual Research Report
  • [Remarks] 脱分化脂肪細胞を細胞原とする再生医療

    • Related Report
      2019 Annual Research Report
  • [Remarks] 脱分化脂肪細胞を細胞源とする再生医療

    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 変形性関節症の予防又は治療剤、及び変形性関節症の予防または治療用薬物組成物2019

    • Inventor(s)
      松本太郎, 遠藤則行, 風間智彦
    • Industrial Property Rights Holder
      学校法人 日本大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-206493
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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