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Pathologic analysis of MODY using pancreatic beta cells derived from MODY-iPS cells.

Research Project

Project/Area Number 26860272
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Experimental pathology
Research InstitutionNational Center for Global Health and Medicine

Principal Investigator

Yabe Shigeharu  国立研究開発法人国立国際医療研究センター, その他部局等, 研究員 (40533716)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords糖尿病 / 膵β細胞 / iPS細胞 / 疾患iPS / MODY
Outline of Final Research Achievements

We established a six-stage protocol mimicking the developmental processes of pancreatic beta cells for the differentiation of human iPSC to pancreatic beta cells using defined culture media without feeders or serum . Spheroid formation at the pancreatic beta cells stage showed more efficient insulin secretion than did monolyater culture. Cultured cells were transpranted under kidney capsules of streptozotocin-induced diabetic NOD/SCID mice. After cell trans plantation, diabetic mice had lower blood glucose levels, and islet-like struture were detected in vivo. Moreover, 12 weeks after transplantation, Human C-peptide was detected in the mouse serum .Tthese results indicated that iPS-beta cells fanctioned in vio.
We also established the iPSC from Maturity-onset diabetes of the young (MODY) 5 patient. In the course of differentiation from MODY5-iPS cells into pancratic beta cells, we found that the amount of mutant transcripts was much less than that of wild one.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (8 results)

All 2016 2015 2014

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 2 results,  Open Access: 2 results) Presentation (2 results) Book (2 results)

  • [Journal Article] Efficient Generation of Functional Pancreatic β Cells from Human iPS Cells2016

    • Author(s)
      Yabe SG, Fukuda S, Takeda F, Nashiro K and Okochi H.
    • Journal Title

      Journal of Diabetes

      Volume: in press Issue: 2 Pages: 168-179

    • DOI

      10.1111/1753-0407.12400

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Establishment of Maturity Onset Diabetes of the Young (MODY)-iPS cells from Japanese patient2015

    • Author(s)
      Yabe SG, Iwasaki N, Yasuda K, Hamazaki TS, Konno M et al.
    • Journal Title

      Journal of Diabetes Investigation

      Volume: in press Issue: 5 Pages: 543-547

    • DOI

      10.1111/jdi.12334

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Safety assessment of bone marrow derived MSC grown in platelet-rich plasma2015

    • Author(s)
      Fukuda S, Hagiwara S, Fukuda S, Yakabe R, Suzuki H, Yabe SG et al.
    • Journal Title

      Regenerative Therapy

      Volume: 1 Pages: 72-79

    • DOI

      10.1016/j.reth.2015.02.001

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Murine Insulinoma Cell-Conditioned Medium with BETA2/Neurod1 Transduction Efficiently Induces the Differentiation of Adipose-Drived Mesenchymal Stem Cells into β-Like Cells both In Vitro and In Vivo2014

    • Author(s)
      Kawamoto K, Yabe S, Konno M et al.
    • Journal Title

      Journal of Stem Cell Research & Therapy

      Volume: 4 Pages: 221-230

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ヒトiPS細胞から機能的膵β細胞(iPS-beta)の分化誘導2016

    • Author(s)
      矢部茂治、福田沙月、霜田雅之、大河内仁志
    • Organizer
      第15回日本再生医療学会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2016-03-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] 遺伝性糖尿病 (MODY)患者由来iPS細胞の膵β細胞分化過程におけるNMDによるMODY変異mRNAの分解2015

    • Author(s)
      矢部茂治・岩崎直子・安田和基・浜崎辰夫・福田沙月・大河内仁志
    • Organizer
      第12回日本再生医療学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2015-03-19
    • Related Report
      2014 Research-status Report
  • [Book] 膵島の再生医療ー膵β細胞の発生と再生をめぐる新展開ー第2章5 疾患iPS技術を利用した遺伝子性糖の解明と再生2015

    • Author(s)
      矢部茂治、大河内仁志
    • Publisher
      診断と治療社
    • Related Report
      2015 Annual Research Report
  • [Book] 膵島の再生医療-膵β細胞の発生と再生をめぐる新展開-第2章5 疾患iPS技術を利用した遺伝性糖尿病の解明と再生2015

    • Author(s)
      矢部茂治、大河内仁志
    • Publisher
      診断と治療社
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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