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Search for innovative organ transplantation without the need for relatives or HLA matching

Research Project

Project/Area Number 19K22648
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
Research InstitutionTohoku University

Principal Investigator

DEZAWA Mari  東北大学, 医学系研究科, 教授 (50272323)

Project Period (FY) 2019-06-28 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsMuse細胞 / 多能性幹細胞 / 免疫抑制 / 免疫寛容 / 点滴 / 他家移植 / 臓器移植
Outline of Research at the Start

Muse細胞は免疫抑制剤の投与が無いにも関わらず、レシピエントの傷害組織内において機能的な分化細胞として半年以上生存が維持される。予備実験においてドナー由来Muse細胞を予め血管内に投与すると骨髄にホーミングし、それに続き同一のドナーの組織を移植すると、免疫抑制剤が無くても拒絶を免れ長期間生着する。従ってドナーMuse細胞を予め点滴で投与しておけば、血縁者やHLA適合の臓器でなくても免疫拒絶を受けずに長期間移植臓器が生着可能となることを示唆する。本研究ではMuse細胞の免疫調整能を検証し、動物移植モデルにおいて「血縁者やHLA適合から解放される新しい移植医療システム」が構築できるかを探索する。

Outline of Final Research Achievements

Muse cells are immune privileged-endogenous pluripotent stem cells. Clinical trials have been conducted by intravenous drip of donor-Muse cells without HLA matching nor immunosuppressant treatment. When donor-Muse cells were intravenously injected prior to the donor-skin transplantation, donor-skin was engrafted at 4 weeks even without immunosuppressant treatment. When B6 mouse-derived Muse cells were intravenously administered to BALB/c mice and then B6-derived bone marrow cells were transplanted to BALB/c mice, B6-hematopoietic stem cells were successfully engraftment until 20 weeks without immunosuppressant. Interestingly, in mice, MDSCs involved in immunosuppression were mobilized from the bone marrow and accumulated in the thymus and spleen. The increase of Treg number in the bone marrow and the accumulation in the spleen were also confirmed. The use of this mechanism may enable transplantation of cells and organs without HLA-matching and immunosuppressant treatment.

Academic Significance and Societal Importance of the Research Achievements

Muse細胞には、傷害部位で修復に当たったMuse細胞を排除しないで長期間受容できるように、骨髄でレシピエントの免疫系に作用する機構がある。という推察が実証されれば、画期的な医療の変革が可能となる。それは、健常ドナーのMuse細胞を臓器移植の前に予め患者に点滴し、その後臓器移植を行えば、免疫拒絶もなく長期間臓器がレシピエントの体内で維持できるということを意味する。
現在の移植医療では、血縁者やHLAの合致を前提とするが、ドナーMuse細胞の事前の点滴を行うことで移植医療をこれらの条件から解放することができる。移植医療ではドナー不足などの問題があるが、その解決にも大きく働く可能性が期待される

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (42 results)

All 2021 2020 2019

All Journal Article (10 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 10 results,  Open Access: 9 results) Presentation (32 results) (of which Int'l Joint Research: 10 results,  Invited: 31 results)

  • [Journal Article] Comparison of separation methods for tissue-derived extracellular vesicles in the liver, heart, and skeletal muscle2021

    • Author(s)
      Matejovic A, Wakao S, Kitada M, Kushida Y, Dezawa M
    • Journal Title

      FEBS Open Bio

      Volume: 11 Issue: 2 Pages: 482-493

    • DOI

      10.1002/2211-5463.13075

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Protection of liver sinusoids by intravenous administration of human Muse cells in a rat extra‐small partial liver transplantation model2021

    • Author(s)
      Shono Yoshihiro、Kushida Yoshihiro、Wakao Shohei、Kuroda Yasumasa、Unno Michiaki、Kamei Takashi、Miyagi Shigehito、Dezawa Mari
    • Journal Title

      American Journal of Transplantation

      Volume: Online ahead of print Issue: 6 Pages: 2025-2039

    • DOI

      10.1111/ajt.16461

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intravenous Injection of Muse Cells as a Potential Therapeutic Approach for Epidermolysis Bullosa2021

    • Author(s)
      Fujita Yasuyuki、Komatsu Miho、Lee San Eun、Kushida Yoshihiro、Nakayama-Nishimura Chihiro、Matsumura Wakana、Takashima Shota、Shinkuma Satoru、Nomura Toshifumi、Masutomi Naoya、Kawamura Makoto、Dezawa Mari、Shimizu Hiroshi
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 141 Issue: 1 Pages: 198-202.e6

    • DOI

      10.1016/j.jid.2020.05.092

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intravenously delivered multilineage-differentiating stress enduring cells dampen excessive glutamate metabolism and microglial activation in experimental perinatal hypoxic ischemic encephalopathy2020

    • Author(s)
      Suzuki Toshihiko、Sato Yoshiaki、Kushida Yoshihiro、Tsuji Masahiro、Wakao Shohei、Ueda Kazuto、Imai Kenji、Iitani Yukako、Shimizu Shinobu、Hida Hideki、Temma Takashi、Saito Shigeyoshi、Iida Hidehiro、Mizuno Masaaki、Takahashi Yoshiyuki、Dezawa Mari、Borlongan Cesar V、Hayakawa Masahiro
    • Journal Title

      Journal of Cerebral Blood Flow & Metabolism

      Volume: 0 Issue: 7 Pages: 1-14

    • DOI

      10.1177/0271678x20972656

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Therapeutic benefit of Muse cells in a mouse model of amyotrophic lateral sclerosis2020

    • Author(s)
      Yamashita Toru、Kushida Yoshihiro、Wakao Shohei、Tadokoro Koh、Nomura Emi、Omote Yoshio、Takemoto Mami、Hishikawa Nozomi、Ohta Yasuyuki、Dezawa Mari、Abe Koji
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 17102-17102

    • DOI

      10.1038/s41598-020-74216-4

    • NAID

      120006900786

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The evaluation of the safety and efficacy of intravenously administered allogeneic multilineage-differentiating stress-enduring cells in a swine hepatectomy model2020

    • Author(s)
      Iseki Masahiro、Mizuma Masamichi、Wakao Shohei、Kushida Yoshihiro、Kudo Katsuyoshi、Fukase Masahiko、Ishida Masaharu、Ono Tomoyuki、Shimura Mitsuhiro、Ise Ichiro、Suzuki Yukie、Sueta Teruko、Asada Ryuta、Shimizu Shinobu、Ueno Yoshiyuki、Dezawa Mari、Unno Michiaki
    • Journal Title

      Surgery Today

      Volume: 51 Issue: 4 Pages: 634-650

    • DOI

      10.1007/s00595-020-02117-0

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell-Based Therapy for Stroke2020

    • Author(s)
      Park You Jeong、Niizuma Kuniyasu、Mokin Maxim、Dezawa Mari、Borlongan Cesar V.
    • Journal Title

      Stroke

      Volume: 51 Issue: 9 Pages: 2854-2862

    • DOI

      10.1161/strokeaha.120.030618

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intravenously Transplanted Human Multilineage-Differentiating Stress-Enduring Cells Afford Brain Repair in a Mouse Lacunar Stroke Model.2020

    • Author(s)
      Abe T, Aburakawa D, Niizuma K, Iwabuchi N, Kajitani T, Wakao S, Kushida Y, Dezawa M, Borlongan CV, Tominaga T.
    • Journal Title

      Stroke.

      Volume: 51(2) Issue: 2 Pages: 601-611

    • DOI

      10.1161/strokeaha.119.026589

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rescue from Stx2-Producing E. coli-Associated Encephalopathy by Intravenous Injection of Muse Cells in NOD-SCID Mice.2020

    • Author(s)
      Ozuru R, Wakao S, Tsuji T, Ohara N, Matsuba T, Amuran MY, Isobe J, Iino M, Nishida N, Matsumoto S, Iwadate K, Konishi N, Yasuda K, Tashiro K, Hida M, Yadoiwa A, Kato S, Yamashita E, Matsumoto S, Kurozawa Y, Dezawa M, Fujii J.
    • Journal Title

      Mol Ther.

      Volume: 28(1) Issue: 1 Pages: 100-118

    • DOI

      10.1016/j.ymthe.2019.09.023

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Quantitative Analysis of SSEA3+ Cells from Human Umbilical Cord after Magnetic Sorting.2019

    • Author(s)
      Leng Z, Sun D, Huang Z, Tadmori I, Chiang N, Kethidi N, Sabra A, Kushida Y, Fu YS, Dezawa M, He X, Young W.
    • Journal Title

      Cell Transplant.

      Volume: 28(7) Issue: 7 Pages: 907-923

    • DOI

      10.1177/0963689719844260

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Medical innovation by non-tumorigenic reparative pluripotent Muse cells2021

    • Author(s)
      Mari Dezawa
    • Organizer
      International Association of Neurorestoratology(IANR)XIII Conference
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Multilineage differentiating stress enduring (Muse) cells2021

    • Author(s)
      Mari Dezawa
    • Organizer
      The International Master’s program in “Regenerative Medicine and Tissue Engineering”
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Muse細胞がもたらす未来の医療2021

    • Author(s)
      出沢 真理
    • Organizer
      2021薬物動態談話会セミナー
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Medical innovation by endogenous pluripotent Muse cells; recent advances of basic research and clinical trials2021

    • Author(s)
      Mari Dezawa
    • Organizer
      the 13th Pan Pacific Symposium on Stem Cells and Cancer Research(PPSSC 2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Muse細胞のもたらす医療イノベーション2021

    • Author(s)
      出沢 真理
    • Organizer
      第57回日本移植学会総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Challenge to medical innovation by non-tumorigenic endogenous reparative Muse cells2021

    • Author(s)
      Mari Dezawa
    • Organizer
      Federation of Stem Cell Associations First International STEMNET MEETING
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Muse細胞のもたらす医療イノベーション2021

    • Author(s)
      出沢 真理
    • Organizer
      第5回学術推進会議
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Muse細胞のもたらす医療イノベーション2021

    • Author(s)
      出沢 真理
    • Organizer
      弘前大学・整形外科学Ⅱ
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Muse細胞のもたらす医療イノベーション2021

    • Author(s)
      出沢 真理
    • Organizer
      第42回日本臨床薬理学会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Muse細胞のもたらす新しい医療2021

    • Author(s)
      出沢真理
    • Organizer
      第20回日本再生医療学会学術総会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Muse細胞のもたらす新しい医療2021

    • Author(s)
      出沢真理
    • Organizer
      第94回日本細菌学会総会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Muse細胞のもたらす次世代の修復医療2021

    • Author(s)
      出沢真理
    • Organizer
      第126回日本解剖学会総会・全国学術集会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Muse細胞の作る未来の医療2020

    • Author(s)
      出沢真理
    • Organizer
      21世紀先端医療コンソーシアム
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Muse細胞による医療イノベーションへの挑戦2020

    • Author(s)
      出沢真理
    • Organizer
      第61回日本神経学会学術大会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Muse細胞を用いた医療イノベーションへの挑戦2020

    • Author(s)
      出沢真理
    • Organizer
      第30回日本医療薬学会年会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 再生医学とMuse細胞2020

    • Author(s)
      出沢真理
    • Organizer
      弘前大学整形外科特別講義
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Muse細胞による医療イノベーションの可能性2020

    • Author(s)
      出沢 真理
    • Organizer
      第125回日本解剖学会学術総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Muse細胞と臨床応用2020

    • Author(s)
      出沢 真理
    • Organizer
      第19回日本再生医療学会総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Challenge to medical innovation by non-tumorigenic pluripotent Muse cells2019

    • Author(s)
      Mari Dezawa
    • Organizer
      Taiwan Healthcare Expo 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Muse細胞を用いた医療イノベーションへの挑戦2019

    • Author(s)
      出沢 真理
    • Organizer
      第72回日本細菌学会中国・四国支部総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Aiming for a Medical Renaissance by Clinical Trials of Endogenous Reparative Pluripotent Muse cells2019

    • Author(s)
      Mari Dezawa
    • Organizer
      Health Span Hawaii Summit
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Challenge to medical innovation by Muse cells2019

    • Author(s)
      Mari Dezawa
    • Organizer
      The 3rd Vinmec Intl. Conference in Hanoi, Vietnam
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Muse細胞のもたらす医療イノベーションへの挑戦2019

    • Author(s)
      出沢 真理
    • Organizer
      第64回日本口腔外科学会総会学術大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Muse細胞による医療イノベーションの可能性2019

    • Author(s)
      出沢 真理
    • Organizer
      千葉大学開講130年記念
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Muse細胞を用いた新しい再生医療について2019

    • Author(s)
      出沢 真理
    • Organizer
      第43回日本血液事業学会総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Muse細胞のもたらす新しい治療概念2019

    • Author(s)
      出沢 真理
    • Organizer
      第59回日本臨床化学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 生体内修復幹細胞 Muse細胞による医療イノベーションへの挑戦2019

    • Author(s)
      出沢 真理
    • Organizer
      再生医療イノベーションフォーラム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Muse細胞のもたらす新しい治療戦略:修復幹細胞治療2019

    • Author(s)
      出沢 真理
    • Organizer
      第92回日本整形外科学会学術総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Muse細胞の発見と医療ルネッサンスへの挑戦(Aiming for a Medical Renaissance by Clinical Trials of Endogenous Reparative Pluripotent Muse cells)2019

    • Author(s)
      出沢 真理
    • Organizer
      第92回日本内分泌学会学術総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Future of Regenerative Medicine and Immune Therapy for Cancer2019

    • Author(s)
      Mari Dezawa
    • Organizer
      Pan Pacific Symposium on Stem Cells and Cancer Research(PPSSC)2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Strategy for Clinical Trials of Muse Cells, Endogenous Reparative Pluripotent Stem Cells2019

    • Author(s)
      Mari Dezawa
    • Organizer
      Pan Pacific Symposium on Stem Cells and Cancer Research(PPSSC)2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Removing barriers of regenerative medicine and promoting innovation connections by discovery of human endogenous pluripotent Muse cells2019

    • Author(s)
      Mari Dezawa
    • Organizer
      the 2019 National Academy of Inventors Annual Meeting(NAI 8th Annual Meeting)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-07-04   Modified: 2023-01-30  

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