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Mechanism based development of differentiation method for pancreatic bud-like cells from human pluripotent stem cells

Research Project

Project/Area Number 15K09385
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionKyoto University

Principal Investigator

Toyoda Taro  京都大学, iPS細胞研究所, 講師 (60593530)

Co-Investigator(Renkei-kenkyūsha) OSAFUNE Kenji  京都大学, iPS細胞研究所, 教授 (80502947)
WATANABE Akira  京都大学, iPS細胞研究所, 特定拠点助教 (60506765)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsNKX6.1 / PDX1 / 膵臓 / iPS細胞 / ES細胞 / 細胞骨格 / 糖尿病 / β細胞 / インスリン / 膵芽 / 発生
Outline of Final Research Achievements

Pancreatic bud/epithelial cells (NKX6.1+ cells) are considered as pancreas-committed cells. Induction of the NKX6.1+ cell is a critical step for the generation of pancreatic cells from human pluripotent stem cells. However, the induction method and mechanism have not yet been fully established. In this study, we identified low molecular weight compounds which promote differentiation into NKX6.1+ cells from human iPS cells. Based on the analysis of the compounds, we found that cytoskeleton regulating molecules are involved in the part of the mechanisms. Our differentiation protocol established in this study and the mechanism may be useful for both basic research and clinical application using pancreatic cells.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (29 results)

All 2017 2016 2015 Other

All Journal Article (10 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (13 results) (of which Int'l Joint Research: 6 results) Book (2 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Small molecule AT7867 proliferates PDX1-expressing pancreatic progenitor cells derived from human pluripotent stem cells2017

    • Author(s)
      Kimura Azuma、Toyoda Taro、Nishi Yohei、Nasu Makoto、Ohta Akira、Osafune Kenji
    • Journal Title

      Stem Cell Research

      Volume: 24 Pages: 61-68

    • DOI

      10.1016/j.scr.2017.08.010

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rho-Associated Kinases and Non-muscle Myosin IIs Inhibit the Differentiation of Human iPSCs to Pancreatic Endoderm2017

    • Author(s)
      Toyoda Taro、Kimura Azuma、Tanaka Hiromi、Ameku Tomonaga、Mima Atsushi、Hirose Yurie、Nakamura Masahiro、Watanabe Akira、Osafune Kenji
    • Journal Title

      Stem Cell Reports

      Volume: 9 Issue: 2 Pages: 419-428

    • DOI

      10.1016/j.stemcr.2017.07.005

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 膵臓・膵島再生研究の現状と展望2017

    • Author(s)
      伊藤遼、豊田太郎、稲垣暢也、長船健二
    • Journal Title

      胆と膵

      Volume: 38 Pages: 879-884

    • Related Report
      2017 Annual Research Report
  • [Journal Article] ES/iPS細胞を用いた膵島再生療法の現状と展望2017

    • Author(s)
      廣瀬友里恵、豊田太郎、長船健二
    • Journal Title

      内分泌・糖尿病・代謝内科

      Volume: 44 Pages: 130-135

    • Related Report
      2016 Research-status Report
  • [Journal Article] iPS細胞を用いた糖尿病の細胞療法への取り組み2017

    • Author(s)
      豊田太郎、中村剛士、田上寛、長船健二
    • Journal Title

      実験医学増刊「糖尿病」

      Volume: 35 Pages: 175-179

    • Related Report
      2016 Research-status Report
  • [Journal Article] iPS細胞を用いた糖尿病に対する再生医療開発2016

    • Author(s)
      天久朝廷、豊田太郎、長船健二
    • Journal Title

      月間糖尿病

      Volume: 8 Pages: 30-37

    • Related Report
      2016 Research-status Report
  • [Journal Article] iPS細胞と糖尿病-移植用膵細胞の再生2016

    • Author(s)
      美馬淳志、豊田太郎、妹尾浩、長船健二
    • Journal Title

      G.I.Reserch

      Volume: 24 Pages: 24-29

    • Related Report
      2016 Research-status Report
  • [Journal Article] 膵β細胞の再生 ―最近の進歩―2016

    • Author(s)
      伊藤遼、豊田太郎、稲垣暢也、長船健二
    • Journal Title

      最新医学

      Volume: 71 Pages: 457-462

    • NAID

      40020761318

    • Related Report
      2015 Research-status Report
  • [Journal Article] iPS細胞から再生膵β細胞2015

    • Author(s)
      木村東、豊田太郎、長船健二
    • Journal Title

      腎と透析

      Volume: 79 Pages: 955-959

    • Related Report
      2015 Research-status Report
  • [Journal Article] インスリン分泌を回復させる iPS細胞の可能性2015

    • Author(s)
      美馬淳志、豊田太郎、長船健二
    • Journal Title

      糖尿病診療マスター

      Volume: 13 Pages: 925-930

    • Related Report
      2015 Research-status Report
  • [Presentation] Rho-associated kinases and non-muscle myosin IIs inhibit the differentiation of human iPSCs to pancreatic endoderm2017

    • Author(s)
      Toyoda T, Kimura A, Tanaka H, Ameku T, Mima A, Hirose Y, Nakamura M, Watanabe A, Osafune K.
    • Organizer
      CiRA 2017 International Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] RHO-ASSOCIATED KINASES AND NON-MUSCLE MYOSIN IIS PLAY INHIBITORY ROLES FOR THE DIFFERENTIATION OF HUMAN IPSCS TO PANCREATIC ENDODERM CELLS2017

    • Author(s)
      Toyoda T, Kimura A, Tanaka H, Ameku T, Mima A, Hirose Y, Nakamura M, Watanabe A, Osafune K.
    • Organizer
      Annual Meeting, International Society for Stem Cell Research 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Small molecule-induced in vitro expansion of PDX1(+) pancreatic progenitor cells2017

    • Author(s)
      Kimura A, Toyoda T, Nishi Y, Nasu M, Ohta A, Osafune K.
    • Organizer
      Kyoto Diabetes Mini-Symposium - Beta-Cell Replacement Strategies
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Insights into the regulatory mechanisms for the differentiation of human iPSCs to pancreatic endoderm cells2017

    • Author(s)
      Toyoda T, Kimura A, Ameku A, Mima A, Osafune K
    • Organizer
      Kyoto Diabetes Mini-Symposium - Beta-Cell Replacement Strategies
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒトiPS/ES細胞から膵芽細胞への分化過程における細胞骨格調節分子の役割2017

    • Author(s)
      豊田太郎、木村東、田中ひろみ、天久朝廷、美馬淳志、廣瀬友里恵、中村正裕、渡辺亮、長船健二
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 劇症1型糖尿病患者由来iPS細胞を用いた膵β細胞傷害機構の解明2016

    • Author(s)
      細川吉弥、豊田太郎、福井健司、馬殿恵、須藤智美、岩橋博見、岸田真里菜、岡田千尋、渡辺亮、浅香勲、長船健二、今川彰久、下村伊一郎
    • Organizer
      第59回日本糖尿病学会年次学術集会
    • Place of Presentation
      京都
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒトiPS細胞から膵内分泌前駆細胞への分化を促進する低分子化合物クロモグリク酸ナトリウムの作用機序の解明2016

    • Author(s)
      伊藤遼、近藤恭士、豊田太郎、舩戸道徳、細川吉弥、須藤智美、庄暁桐、太田章、稲垣暢也、長船健二
    • Organizer
      第59回日本糖尿病学会年次学術集会
    • Place of Presentation
      京都
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report
  • [Presentation] 再生医療応用に向けたヒトiPS細胞由来膵系譜細胞の増殖促進因子の探索2016

    • Author(s)
      木村東、豊田太郎、田中ひろみ、西洋平、太田章、長船健二
    • Organizer
      第59回日本糖尿病学会年次学術集会
    • Place of Presentation
      京都
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report
  • [Presentation] 再生医療応用に向けたヒトiPS細胞から膵芽細胞への分化機序解明2016

    • Author(s)
      豊田太郎、木村東、田中ひろみ、美馬淳志、廣瀬友里恵、渡辺亮、長船健二
    • Organizer
      第59回日本糖尿病学会年次学術集会
    • Place of Presentation
      京都
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report
  • [Presentation] Identification of proliferation promoting factors for hiPSC-derived pancreatic progenitor cells2016

    • Author(s)
      Kimura A, Toyoda T, Tanaka H, Nishi Y, Ohta A, Osafune K
    • Organizer
      CiRA/ISSCR International Symposium 2016
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2016-03-22
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 糖尿病に対する細胞療法確立に向けたヒトiPS細胞由来膵系譜細胞の増殖促進因子の探索2016

    • Author(s)
      木村東、豊田太郎、長船健二
    • Organizer
      第15回日本再生医療学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2016-03-17
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒトiPS細胞から膵内分泌前駆細胞への分化を促進する低分子化合物の同定2015

    • Author(s)
      近藤恭士、豊田太郎、舩戸道徳、細川吉弥、須藤智美、庄暁桐、太田章、山中伸弥、稲垣暢也、長船健二
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      山口
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] 劇症1型糖尿病特異的iPS細胞の樹立とインスリン産生細胞への分化誘導2015

    • Author(s)
      細川吉弥、豊田太郎、福井健司、浅香勲、馬殿恵、須藤智美、岩橋博見、長船健二、今川彰久、下村伊一郎
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      山口
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Book] 「再生医療」小児・思春期糖尿病コンセンサス・ガイドライン2015

    • Author(s)
      豊田太郎、長船健二
    • Total Pages
      315
    • Publisher
      南江堂
    • Related Report
      2015 Research-status Report
  • [Book] 「再生医学・iPS細胞」糖尿病学2015

    • Author(s)
      近藤恭士、豊田太郎、稲垣暢也、長船健二
    • Total Pages
      623
    • Publisher
      西村書店
    • Related Report
      2015 Research-status Report
  • [Remarks] ヒトES/iPS細胞由来の膵前駆細胞を特異的に増殖促進する低分子化合物を同定

    • URL

      http://www.cira.kyoto-u.ac.jp/j/pressrelease/news/170823-140000.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] ヒトiPS細胞から膵臓細胞への分化を制御するメカニズムの一端を解明

    • URL

      http://www.cira.kyoto-u.ac.jp/j/pressrelease/news/170809-083000.html

    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 膵芽細胞の製造方法2015

    • Inventor(s)
      長船健二/豊田太郎/木村東
    • Industrial Property Rights Holder
      長船健二/豊田太郎/木村東
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-185662
    • Filing Date
      2015-09-18
    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] 長船健二、豊田太郎2015

    • Inventor(s)
      膵芽細胞の製造方法および膵芽細胞を含む膵疾患治療剤
    • Industrial Property Rights Holder
      膵芽細胞の製造方法および膵芽細胞を含む膵疾患治療剤
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-05-20
    • Related Report
      2015 Research-status Report
    • Overseas

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Published: 2015-04-16   Modified: 2019-03-29  

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