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Development of inflamed pancreatic islet tissues using human iPS cells derived pancreatic cells

Research Project

Project/Area Number 18K18359
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 90110:Biomedical engineering-related
Research InstitutionThe University of Tokyo

Principal Investigator

Shinohara Marie  東京大学, 生産技術研究所, 助教 (00789133)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords膵島 / 炎症 / マクロファージ / 凝集体 / 糖尿病 / インスリン / 酸素 / マイクロウェル / ヒトiPS細胞
Outline of Final Research Achievements

In this study, a culture system was developed that reproduces in vitro cell death of pancreatic β-cells and infiltration of immune cells into the islets, which caused by the inflammation. After formation of pancreatic islet-like aggregates using several kinds of endocrine pancreas cells on a plate with microwells on the bottom surface. The inflammation was induced by IL-1β and IFN-γ stimulation, and co-culture with macrophages was performed. IL-1β stimulation of pancreatic β cells increased the productivity of inflammatory factors such as CCL2 and CCL3, and co-culture with macrophages markedly caused apoptosis and cell death. It was suggested that pancreatic β-cell damage could be reproduced by IL-1β stimulation from macrophages in vitro.

Academic Significance and Societal Importance of the Research Achievements

糖尿病研究や新規糖尿病治療薬の開発において,専ら動物実験や動物由来の初代膵島を用いた検討が行われているが,ヒトでの生理的な応答を十分に再現することは難しい. そして,初代培養では単離後に機能が著しく低下するため,評価系として均質性を維持することは困難である.本研究の成果は,生体内の炎症による膵β細胞の細胞死と機能障害を再現する膵島組織培養の可能性を示すものであり,ヒトiPS細胞由来膵島構成細胞や細胞株など様々な細胞種に応用が可能であることから,糖尿病研究や創薬分野の加速化につながることが期待される.

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (6 results)

All 2020 2019

All Journal Article (2 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Endodermal differentiation of human induced pluripotent stem cells using simple dialysis culture system in suspension culture2019

    • Author(s)
      Marie Shinohara, Hyunjin Choi, Masato Ibuki, Shigeharu G.Yabe, Hitoshi Okochi, Atsushi Miyajimam Yasuyuki Sakai
    • Journal Title

      Regenerative Therapy

      Volume: 12 Pages: 14-19

    • DOI

      10.1016/j.reth.2019.05.004

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Present status of large-scale culture methods of pluripotent stem cell : Differentiation of human iPS cells with dialysis suspension culture2019

    • Author(s)
      チェ ヒョンジン、篠原 満利恵、酒井 康行
    • Journal Title

      Organ Biology

      Volume: 26 Issue: 2 Pages: 175-184

    • DOI

      10.11378/organbio.26.175

    • NAID

      130007716018

    • ISSN
      1340-5152, 2188-0204
    • Related Report
      2019 Annual Research Report
  • [Presentation] ヒトiPS細胞由来膵β細胞凝集体の効率的調製のための透析浮遊培養2020

    • Author(s)
      チェ ヒョンジン,酒井 康行, 篠原 満利恵
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Macrophage aceralates inflamemation of pancreastic β-cell aggregates2019

    • Author(s)
      Marie Shinohara, Thalia Nghiem, Qiao You Lau, Fumiya Tokitou, and Yasuyuki Sakai
    • Organizer
      microTAS2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 酸素透過性多孔質担体を用いた膵島様組織培養2019

    • Author(s)
      時任文弥,篠原満利恵,丸山優史,酒井康行,大竹勝人
    • Organizer
      化学工学会第84年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Cost-effective differentiation of human iPS cells to pancreatic β-cells based on aggregate suspension culture with dialysis operations2019

    • Author(s)
      Hyunjin Choi, Marie Shinohara, Yasuyuki Sakai
    • Organizer
      ISSCR 17th Annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2021-12-27  

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