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Development of the differentiation derivative methods from induced tissue-specific pancreatic stem cells using TASCL to insulin excretory cells

Research Project

Project/Area Number 19K09051
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionUniversity of the Ryukyus

Principal Investigator

SHIOHIRA CHIKA  琉球大学, 医学(系)研究科(研究院), 助教 (50325833)

Co-Investigator(Kenkyū-buntansha) 野口 洋文  琉球大学, 医学(系)研究科(研究院), 教授 (50378733)
池内 真志  東京大学, 大学院情報理工学系研究科, 講師 (90377820)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords組織特異的幹細胞 / iTS-P / TASCL / 3次元培養 / マイクロデバイス / インスリン分泌細胞 / 糖尿病マウス / 血糖降下作用 / 組織特異的膵幹細胞 / インスリン分泌細胞分化誘導法 / TASCL / 三次元培養
Outline of Research at the Start

幹細胞からインスリン分泌細胞への効率の高い分化誘導効法の開発は未だ途上段階である。我々は組織特異的膵幹細胞:iTS-P細胞において2次元培養よりも、スフェロイド培養(3次元培養)がインスリン分泌細胞への分化誘導効率がよいことを報告した(Miyagi-Shiohira C et al. Sci Rep(IF:4.122))。しかしiTS-P細胞のスフェロイドのサイズが不均一であると分化誘導効率も一定ではないという欠点があった。マイクロデバイスTASCLは均一で目的のサイズのスフェロイドを多量に作成することが可能であり、インスリン分泌細胞の分化誘導効率の向上に有効であると考えられる。

Outline of Final Research Achievements

In this study, we succeeded in producing the cell mass of artificial insulin excretory cells from induced tissue specific pancreatic stem (iTS-P) cells using microdevice TASC. We were posssible to make the cell mass which is necessary for transplantation in large quantities concurrently. Furthermore, we transplanted the insulin excretory cells under the capsule of the kidney of diabetes mouse and confirmed a diachronic descent effect of the blood glucose level.

Academic Significance and Societal Importance of the Research Achievements

ES/iPS細胞からインスリン分泌細胞への分化誘導を行う研究は数多くあるが、分化誘導効率が低いのが現状である。iTS細胞研究においては、研究代表者の施設が先駆的に行っており世界をリードしている。また、研究分担者の池内は、均一胚葉体を一度に大量に作製でき、その胚葉体の形状やサイズをコントロールするマイクロデバイスTASCLを作製し特許を取得している。本研究においてインスリン分泌細胞を短期間、低コストで効率よく作製するために、我々が樹立したiTS-P細胞とマイクロデバイスTASCLを組み合わせることで血糖降下作用を持った、人工インスリン分泌細胞を効率よく一度に大量に作製することに成功した。

Report

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

    (9 results)

All 2021 2020 2019

All Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 6 results) Presentation (1 results)

  • [Journal Article] In vivo evaluation ofGG2-GG1/ A2 element activity in the insulin promoter region using the CRISPR-Cas9 system2021

    • Author(s)
      Hirofumi Noguchi Chika Miyagi Shiohira Takao Kinjo Issei Saitoh MasamiWatanabe
    • Journal Title

      Scientifc Reports

      Volume: 11:20290 Issue: 1 Pages: 20290-20290

    • DOI

      10.1038/s41598-021-99808-6

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gene Expression in Pancreatic Cancer-Like Cells and Induced Pancreatic Stem Cells Generated by Transient Overexpression of Reprogramming Factors2021

    • Author(s)
      Miyagi-Shiohira Chika、Saitoh Issei、Watanabe Masami、Noguchi Hirofumi
    • Journal Title

      Journal of Clinical Medicine

      Volume: 10 Issue: 3 Pages: 454-454

    • DOI

      10.3390/jcm10030454

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pancreas preservation with amphotericin B deteriorates islet yield for porcine islet isolation2021

    • Author(s)
      Sayaka Sawada Chika Miyagi‐Shiohira Kazuho Kuwae Hirofumi Noguchi
    • Journal Title

      pancreas

      Volume: -

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pancreas Preservation in Modified Histidine-lactobionate Solution Is Superior to That in University of Wisconsin Solution for Porcine Islet Isolation2021

    • Author(s)
      Mayuko Sakai-Yonaha Chika Miyagi-Shiohira Kazuho Kuwae Hirofumi Noguchi
    • Journal Title

      pancreas

      Volume: -

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Kyoto probe-1 reveals phenotypic differences between mouse ES cells and iTS-P cells2020

    • Author(s)
      Miyagi-Shiohira Chika、Saitoh Issei、Watanabe Masami、Noguchi Hirofumi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 945-949

    • DOI

      10.1038/s41598-020-75016-6

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Induction of Expandable Tissue-Specific Progenitor Cells from Human Pancreatic Tissue through Transient Expression of Defined Factors2019

    • Author(s)
      Noguchi Hirofumi、Miyagi-Shiohira Chika、Nakashima Yoshiki、Kinjo Takao、Kobayashi Naoya、Saitoh Issei、Watanabe Masami、Shapiro A. M. James、Kin Tatsuya
    • Journal Title

      Molecular Therapy - Methods & Clinical Development

      Volume: 13 Pages: 243-252

    • DOI

      10.1016/j.omtm.2019.01.011

    • NAID

      120007004859

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of Proteins Differentially Expressed by Adipose-derived Mesenchymal Stem Cells Isolated from Immunodeficient Mice.2019

    • Author(s)
      Nakashima Y, Nahar S, Miyagi-Shiohira C, Kinjo T, Kobayashi N, Kitamura S, Saitoh I, Watanabe M, Fujita J, Noguchi H
    • Journal Title

      Int J Mol Sci

      Volume: 30 Issue: 11 Pages: 1-19

    • DOI

      10.3390/ijms20112672

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Liquid Chromatography with Tandem Mass Spectrometry-Based Proteomic Analysis of Primary Cultured Cells and Subcultured Cells Using Mouse Adipose-Derived Mesenchymal Stem Cells2019

    • Author(s)
      Nakashima Yoshiki、Nahar Saifun、Miyagi-Shiohira Chika、Kinjo Takao、Kobayashi Naoya、Saitoh Issei、Watanabe Masami、Fujita Jiro、Noguchi Hirofumi
    • Journal Title

      Stem Cells International

      Volume: 2019 Pages: 1-97

    • DOI

      10.1155/2019/7274057

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 自律複製型RNAベクターによる人工膵幹細胞(iTS-P)の樹立2019

    • Author(s)
      潮平知佳
    • Organizer
      再生医療学会総会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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