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Multiple Endodermal Organoid Generation from Robustly Amplified Human Posterior Gut Progenitors

Research Project

Project/Area Number 15H06534
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field General surgery
Research InstitutionYokohama City University

Principal Investigator

ZHANG Ranran  横浜市立大学, 医学研究科, 博士研究員 (10760887)

Research Collaborator Taniguchi Hideki  
Takebe Takanori  
Project Period (FY) 2015-08-28 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords幹細胞 / 原始腸内胚葉細胞 / 分化 / 肝臓 / 移植 / PGEC / liver bud / transplantation / pancreas / differentiation / liver / pancreatic / intestine / 多能性幹細胞 / 分化誘導 / 内胚葉細胞
Outline of Final Research Achievements

Early human developmental progenitors naturally possess robust amplification potential to ensure organ growth; thereby, are considered as a promising source for therapy due to minimal risks for tumor or ectopic tissue formation. Here, we first demonstrated the reproducible generation of human CDX2+ posterior gut endoderm cells (PGECs) from multiple induced pluripotent stem cell (iPSC) clones. We were able to amplify storable PGECs over a number of passages up to 1021 cells, showed much more stable differentiation propensity into endodermal lineage cells. Furthermore, human PGECs were capable of producing hepatic and intestinal tissues. PGEC-liver organoid transplantation showed therapeutic potential in treating lethal liver failure. Thus, the use of PGECs may be not only a promising alternative therapeutic source of pluripotency for self-organizing endodermal organoids but also a unique approach to study the developmental biology and disease model of the human gut.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • Research Products

    (4 results)

All 2017 2016

All Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (1 results)

  • [Journal Article] Nutritional modulation of mouse and human liver bud growth through a branched-chain amino acid metabolism.2017

    • Author(s)
      Koike H, Zhang RR, Ueno Y, Sekine K, Zheng YW, Takebe T, Taniguchi H.
    • Journal Title

      Development

      Volume: 144(6) Pages: 1018-1024

    • DOI

      10.1242/dev.143032

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Generation of a Humanized Mouse Liver Using Human Hepatic Stem Cells2016

    • Author(s)
      Zhang RR, Zheng YW, Taniguchi H.
    • Journal Title

      J Vis Exp

      Volume: (114) Issue: 114 Pages: 0-14

    • DOI

      10.3791/54167

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Three-Dimensional Culture Systems and Humanized Liver Models Using Hepatic Stem Cells for Enhanced Toxicity Assessment2016

    • Author(s)
      Ran-Ran Zhang, Yun-Wen Zheng, Hideki Taniguchi
    • Journal Title

      Stem Cells in Toxicology and Medicine

      Volume: 8 Pages: 145-154

    • DOI

      10.1002/9781119135449.ch8

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Generation Of Expandable Endodermal Cells From Human Induced Pluripotent Stem Cells2016

    • Author(s)
      Ran-Ran Zhang, Takanori Takebe, Yun-Wen Zheng, Hideki Taniguchi
    • Organizer
      The 15th Congress of the Japanese Society for Regenerative Medicine
    • Place of Presentation
      大阪国際会議場(大阪府大阪市北区)
    • Year and Date
      2016-03-16
    • Related Report
      2015 Annual Research Report

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Published: 2015-08-26   Modified: 2018-03-22  

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