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Establishment of AML mouse model using human iPSC

Research Project

Project/Area Number 19K16774
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionKyushu University

Principal Investigator

Nii Takenobu  九州大学, 医学研究院, 助教 (10743990)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords白血病 / 骨髄微小環境 / マウスモデル / iPS細胞 / 急性骨髄性白血病 / ヒトiPS細胞 / モデルマウス / AML / MSC
Outline of Research at the Start

がん治療薬の開発及び研究において、がん患者由来細胞を移植したPatient Derived Xenograft(PDX)マウスが注目されている。急性骨髄性白血病(AML)-PDXマウスの作製効率は約50%であり、未だ作製困難なAML患者由来細胞が多く存在する。本研究ではヒトiPS細胞から作製したヒト骨髄微小環境を用いることで、AML-PDXマウスを効率よく作製する方法の開発を行う。

Outline of Final Research Achievements

In this study, we tried to improve efficiency of establishment of acute myeloid leukemia (AML) mouse model using AML patient sample. we used human induced pluripotent stem cell (iPSC) for establishment of human bone marrow microenvironment in mouse because the bone marrow microenvironment are different from between human and mouse. During this project, we analyzed the bone marrow-like tissue derived from human iPSC histologically and transplantation ability of human AML cell in the bone marrow-like tissue.

Academic Significance and Societal Importance of the Research Achievements

当該研究はAML患者細胞の骨髄への生着能を理解する研究のうち、マウスとヒトの骨髄環境の違い、及びヒト骨髄微小環境におけるECの重要性の解明に大きく貢献する初めての報告となりうる。また、本研究で開発された技術はヒトiPS細胞を利用した薬のスクリーニング方法の一つとして産業応用される可能性がある。作製されたAML-PDXマウスを非臨床試験で使用し、臨床試験での再現性が高まることで開発成功率の向上、開発費用の削減につながると考えられ、製薬企業に費用対効果の高い解決策を提供できると考えられる。

Report

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

    (6 results)

All 2021 2020 2019

All Journal Article (5 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] The Bioactive Peptide SL-13R Expands Human Umbilical Cord Blood Hematopoietic Stem and Progenitor Cells In Vitro2021

    • Author(s)
      Nii Takenobu、Konno Katsuhiro、Matsumoto Masaki、Bhukhai Kanit、Borwornpinyo Suparerk、Sakai Kazuhiro、Hongeng Suradej、Sugiyama Daisuke
    • Journal Title

      Molecules

      Volume: 26 Issue: 7 Pages: 1995-1995

    • DOI

      10.3390/molecules26071995

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Establishing a translational research network in the Asia-Pacific Region through Industry-Academia-Government Collaboration: The Japan Medical Innovation Program2020

    • Author(s)
      NII Takenobu、SWAIN Anthony、MINE Yuichi、TAKAI-YUMINE Ayako、SUGIYAMA Daisuke
    • Journal Title

      Translational and Regulatory Sciences

      Volume: 2 Issue: 2 Pages: 42-46

    • DOI

      10.33611/trs.2020-004

    • NAID

      130007889735

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Establishment of a Translational Science and Medicine Training Program in Japan2020

    • Author(s)
      NII Takenobu、SITTAMPALAM Sitta G.、MINE Yuichi、SUGIYAMA Daisuke
    • Journal Title

      Translational and Regulatory Sciences

      Volume: 2 Issue: 2 Pages: 36-41

    • DOI

      10.33611/trs.2020-005

    • NAID

      130007889753

    • ISSN
      2434-4974
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] ipridone ONC212 activates orphan G protein-coupled receptor GPR132 and integrated stress response in acute myeloid leukemia2019

    • Author(s)
      Nii T, Prabhu VV, Ruvolo V, Madhukar N, Zhao R, Mu H, Heese L, Nishida Y, Kojima K, Garnett MJ, McDermott U, Benes CH, Charter N, Deacon S, Elemento O, Allen JE, Oster W, Stogniew M, Ishizawa J, Andreeff M.
    • Journal Title

      Leukemia

      Volume: 33 Issue: 12 Pages: 2805-2816

    • DOI

      10.1038/s41375-019-0491-z

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mitochondrial ClpP-Mediated Proteolysis Induces Selective Cancer Cell Lethality.2019

    • Author(s)
      Ishizawa J, Zarabi SF, Davis RE, Halgas O, Nii T, Jitkova Y, Zhao R, St-Germain J, Heese LE, Egan G, Ruvolo VR, Barghout SH, Nishida Y, Hurren R, Ma W, Gronda M, Link T, Wong K, Mabanglo M, Kojima K, Andreeff M
    • Journal Title

      Cancer Cell

      Volume: 35 Issue: 5 Pages: 721-737

    • DOI

      10.1016/j.ccell.2019.03.014

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] BIOACTIVE PEPTIDE SL-13R EXPANDS HUMAN UMBILICAL CORD BLOOD HEMATOPOIETIC STEM CELLS2019

    • Author(s)
      Takenobu Nii, Katsuhiro Konno, Mami Shigeto, Ayako Kaneyuki, Motoko Sumasu, Toshiyuki Owaki, Daisuke Sugiyama.
    • Organizer
      International Society for Stem Cell Research
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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

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