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Direct conversion for pancreatic beta cell regeneration towards type 1 diabetes

Research Project

Project/Area Number 16K15624
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Digestive surgery
Research InstitutionJuntendo University (2018)
Saitama Medical University (2016-2017)

Principal Investigator

Matsumoto Masahito  順天堂大学, 医学(系)研究科(研究院), 客員准教授 (90321819)

Research Collaborator Okazaki Yasushi  
Yasunami Yoichi  
Sugahara Yzumi  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords分化転換 / 糖尿病 / 再生医学 / 体細胞 / 膵β細胞 / 再生 / 細胞分化 / 直接変換 / シグナル伝達 / ゲノム
Outline of Final Research Achievements

The research purpose is to establish the protocol of making efficiently somatic cells-derived islet-like cells and to improve blood glucose level in type 1 diabetic model transplanted with the cells. We found that somatic cells such as mouse embryonic fibroblasts (MEF) can be efficiently reprogrammed to make islet-like clusters using retrovirus vector system, and transplantation of islet-like cells in the kidney capsule of type 1 diabetic mice administered with streptozotocin (STZ) ameliorated high blood glucose level. Novel protocols not only with retrovirus system but also other safety methods to induce endogenous insulin have established.

Academic Significance and Societal Importance of the Research Achievements

本研究成果により下記の学術的ならびに社会的意義が期待できると考えられる。1)癌化の可能性が低く、安全性が担保される。2)高血糖(インスリン依存性糖尿病)を改善する。3)1型糖尿病患者が生涯を通じて15万回以上インスリン注射と血糖管理の負担から解放できる。4)低血糖による昏睡の心配がなくなる。5)創薬利用;本細胞を使い糖尿病治療薬候補物質のスクリーニングに利用する。6)10歳未満の糖尿病患者では97%がI型糖尿病であるため、生涯を通じて10万回以上インスリン注射と血糖管理の負担から解放することができる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (21 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 6 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] 西オーストラリア大学/University of Western Australia/Harry Perkins Institute(オーストラリア)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] ブリュッセル大学/Vrije Universiteit Brussel(ベルギー)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Expansion of transplanted islets in mice by co-transplantation with adipose tissue-derived mesenchymal stem cells2018

    • Author(s)
      Tanaka Tomoko、Kojima Daibo、Mera Toshiyuki、Matsumoto Masahito、Yasunami Yohichi、Yanase Toshihiko
    • Journal Title

      Heliyon

      Volume: 4 Issue: 5 Pages: e00632-e00632

    • DOI

      10.1016/j.heliyon.2018.e00632

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A new method for identifying mouse pancreatic ducts2018

    • Author(s)
      Nakajima C, Kamimoto K, Miyajima K, Matsumoto M, Okazaki Y, Kobayashi-Hattori K, Shimizu M, Yamane T, Oishi Y, Iwatsuki K.
    • Journal Title

      Tissue Eng.

      Volume: 24 Issue: 8 Pages: 480-485

    • DOI

      10.1089/ten.tec.2018.0127

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential application of testosterone replacement therapy as treatment for obesity and type 2 diabetes in men.2018

    • Author(s)
      Fink J, Matsumoto M, Tamura Y.
    • Journal Title

      Steroids

      Volume: 161 Pages: 161-166

    • DOI

      10.1016/j.steroids.2018.08.002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anabolic-androgenic steroids: procurement and administration practices of doping athletes2018

    • Author(s)
      Fink Julius、Schoenfeld Brad Jon、Hackney Anthony C.、Matsumoto Masahito、Maekawa Takahiro、Nakazato Koichi、Horie Shigeo
    • Journal Title

      The Physician and Sportsmedicine

      Volume: 47 Issue: 1 Pages: 10-14

    • DOI

      10.1080/00913847.2018.1526626

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mobility and biomechanical functions in the aging male : testosterone and the Locomotive Syndrome.2018

    • Author(s)
      Fink J, Jackney A, Matsumoto M, Maekawa T, Nkazato K, Horie S.
    • Journal Title

      Aging Male

      Volume: 29 Issue: 5 Pages: 1-8

    • DOI

      10.1080/13685538.2018.1504914

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differentiation of Islet Progenitors Regulated by Nicotinamide into Transcriptome-Verified β Cells That Ameliorate Diabetes.2017

    • Author(s)
      Jiang FX, Li K, Archer M, Mehta M, Jamieson E, Charles A, Dickinson JE, Matsumoto M, Morahan G
    • Journal Title

      Stem Cells

      Volume: 35 Issue: 5 Pages: 1341-1354

    • DOI

      10.1002/stem.2567

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Functional roles of netrin-1 in osteoblast differentiation. In vivo2017

    • Author(s)
      Sato M, Kokabu S, Enoki Y, Hayashi N, Matsumoto M, Nakahira M, Sugasawa M, Yoda T
    • Journal Title

      In vivo

      Volume: 31 Pages: 321-8

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Netrin-4 Promotes Differentiation and Migration of Osteoblasts2017

    • Author(s)
      Enoki Y, Sato T, Kokabu S, Hayashi N, Iwata T, Yamato M, Usui M, Matsumoto M, Tomoda T, Ariyoshi W, Nishihara T, Yoda T
    • Journal Title

      In vivo

      Volume: 31 Pages: 793-9

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] An inhibitor of Fibroblast Growth Factor Receptor-1 (FGFR1) promotes late-stage terminal differentiation from NGN3+ pancreatic endocrine progenitors2016

    • Author(s)
      Yamashita-Sugahara Y, Matsumoto M, Ohtaka M, Nishimura K, Nakanishi M, Mitani K, Okazaki Y
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 335908-335908

    • DOI

      10.1038/srep35908

    • NAID

      120007129280

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 腸管オルガノイドと生体腸組織における内分泌細胞の比較2019

    • Author(s)
      大木淳子, 坂下陽彦, 稲葉明彦, 粟飯原永太郎, 内山博允, 松本征仁, 二ノ宮裕三, 山根拓実, 大石祐一, 岩槻健
    • Organizer
      日本農芸化学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 細胞分化と直接変換による細胞運命決定のコントロール2019

    • Author(s)
      松本征仁 岡﨑康司
    • Organizer
      H30年度先端モデル動物支援プラットフォーム成果発表会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 低血糖に陥らないヒトバイオ人工膵島の革新的作出法と安全性評価2019

    • Author(s)
      松本征仁 岡﨑康司
    • Organizer
      AMED橋渡し研究戦略的推進プログラム成果発表会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 成熟膵島で抑制されている遺伝子の解析2018

    • Author(s)
      西村 渉, 安田 和基, 松本 征仁, 岡崎 康司, 野田 泰子
    • Organizer
      第61回日本糖尿病学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] in vivo / in vitro双方からの膵臓再生メカニズムの解明2018

    • Author(s)
      中嶋ちえみ, 神元健児, 美谷島克宏, 松本征仁 ,岡崎康司, 山根拓実, 岩槻健, 大石祐一
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ovel approaches for making beta cells towards beta cell replenishment therapy2017

    • Author(s)
      Matsumoto M
    • Organizer
      Kyoto Diabetes Mini-symposium-Beta cell replacement strategies
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] ダイレクトリプログラミングによる体細胞からβ細胞の高効率作出法2016

    • Author(s)
      松本征仁
    • Organizer
      日本IDDMネットワークサイエンスフォーラム
    • Place of Presentation
      佐賀県鳥栖市
    • Year and Date
      2016-06-25
    • Related Report
      2016 Research-status Report
    • Invited
  • [Book] ペプチドを利用した糖尿病・骨代謝疾患の機能再建と再生,医療・診断をささえるペプチド科学-再生医療・DDS・診断への応用 第V編再生治療第5章2017

    • Author(s)
      松本征仁
    • Publisher
      (株)シーエムシー出版
    • ISBN
      9784781312675
    • Related Report
      2017 Research-status Report
  • [Remarks] 糖尿病創薬に光ーインスリン産生細胞の分化マーカーを2色の蛍光で標識したヒトiPS細胞の開発

    • URL

      http://www.saitama-med.ac.jp/genome/z_press%20release/press_release_10_27_16.pdf

    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] 膵内分泌細胞の分化促進と産生法の迅速効率化、および糖尿病治療薬スクリーニング2016

    • Inventor(s)
      松本征仁、岡﨑康司、菅原泉
    • Industrial Property Rights Holder
      松本征仁、岡﨑康司、菅原泉
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-10-28
    • Related Report
      2016 Research-status Report
    • Overseas

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Published: 2016-04-21   Modified: 2025-01-30  

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