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a novel culture method for efficient differentiation of insulin producing cells (IPC) focusing on cell polarity.

Research Project

Project/Area Number 19K18056
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionThe University of Tokushima

Principal Investigator

IWAHASHI Shuichi  徳島大学, 大学院医歯薬学研究部(医学域), 徳島大学専門研究員 (30531751)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsインスリン分泌細胞 / 細胞極性 / 細胞分化誘導 / 脂肪由来幹細胞
Outline of Research at the Start

細胞における極性は正常な組織発生や生理機能に必須であり、Insulin producing cell (IPC) の培養法として確立されている三次元培養においても、細胞極性が分化誘導に重要であると考えられている。しかしながら、そのメカニズムは依然不明な点が多く、さらに効率的な分化のための培養法の確立が期待される。本研究では、細胞極性維持に着目し、MSCからIPCへ効率的な分化のための培養法を確立することを目的とする。

Outline of Final Research Achievements

We assumed that electrical stimulation could enhance cell adhesion and activation of intracellular signal pathways to promote efficiently differentiation of insulin-producing cells (IPCs) for boost up of cell function. The stimulating condition (100 Hz, 200 mV for 72 hours) was determined by previous report, but the number of survival cells significantly decreased. Then, the conditions were changed to mild condition of 1 V / cm, 0.1 ms, 55 pps reported by another previous report. However, electrical stimulation induced excessive ER stress on the cells, and reduced secretion of insulin and expression of ZO-1, which is cell adhesion protein.Electrical stimulation could not enhance differentiation of IPC under this condition. Further investigation is needed for appropriate condition.

Academic Significance and Societal Importance of the Research Achievements

研究代表者はこれまでに間葉系幹細胞(MSC)から膵β細胞様の機能を持つInsulin producing cell(IPC)への分化誘導実験に着手し、Histone deacetylase inhibitorを添加した2 step protocolを確立している。一方で電気刺激が細胞に与える影響として抗細胞死効果や、他細胞への分化が起こることが報告されている。電気刺激の適切な条件を同定することにより、胚葉転換のメカニズム解明やIPCへの効率的な分化誘導が可能となり得ると考えられる。

Report

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

    (2 results)

All 2020 2019

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results)

  • [Journal Article] The Fragility of Cryopreserved Insulin-producing Cells Differentiated from Adipose-tissue-derived Stem Cells.2020

    • Author(s)
      Tokuda K, Ikemoto T, Saito Y, Miyazaki K, Yamashita S, Yamada S, Imura S, Morine Y and Shimada M.
    • Journal Title

      Cell Transplant.

      Volume: 29 Pages: 1-9

    • DOI

      10.1177/0963689720954798

    • NAID

      120007175421

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vitro and in vivo effects of insulin-producing cells generated by xeno-antigen free 3D culture with RCP piece2019

    • Author(s)
      Ikemoto Tetsuya、Feng Rui、Iwahashi Shu-ichi、Yamada Shinichiro、Saito Yu、Morine Yuji、Imura Satoru、Matsuhisa Munehide、Shimada Mitsuo
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 10-759

    • DOI

      10.1038/s41598-019-47257-7

    • NAID

      120006872360

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2019-04-18   Modified: 2022-01-27  

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