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Search for mesenchymal stem cells with high radiation damage healing ability using humanized mouse

Research Project

Project/Area Number 16K10377
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Radiation science
Research InstitutionNational Institutes for Quantum and Radiological Science and Technology

Principal Investigator

Takizawa Kazuya  国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 放射線障害治療研究部, 研究員(任非) (20739388)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords間葉系幹細胞 / 造血幹細胞 / 放射線障害 / ヒト化マウス / iPS細胞
Outline of Final Research Achievements

In this study, we tried to evaluate the protective effects of human mesenchymal stem cells (MSCs) on radiation-induced damage of tissue stem cells, by using humanized mouse model. We tried to generate the humanized mouse model by co-transplantion of human hematopoietic stem cells (HSCs) with human MSCs or transplantation of the human HSCs alone into bone marrow of a hyper immunodeficiency NOG mouse. However, contrary to my expectation, the human HSCs was not detected in peripheral blood of the transplanted mouse at from 4 to 6 months after the transplantation, indicating difficulty of reconstitution of intramedullary hematopoietic microenvironments. In addition, in order to generate MSCs with higher radioprotective effects, MSCs were induced from human iPS cells. The exosomes derived from the induced MSCs (iMSCs) improved the survival rate of irradiated- HSCs in vitro.

Academic Significance and Societal Importance of the Research Achievements

本研究により開発された評価系は、ヒト由来の細胞やタンパク質などとの相互作用がよりヒト生体内での反応を反映したものとなると考えられ、これまでの放射線照射マウス実験系よりも一歩踏み込んだ知見を得られるツールとして、放射線障害治療に向けた創薬基盤などに活用されることが期待できる。
一方で、iPS細胞より作製されたiMSCを解析する事により、これまで多くの報告がなされてきたMSCの多様な組織障害治癒効果をもたらしている生物活性の中心的な作用機序を明らかにすると供に、遺伝子改変等によって目的の組織障害に合せた機能的なMSCを作出する医療的応用への足がかりとなる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (2 results)

All 2018 2016

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results)

  • [Journal Article] Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites2018

    • Author(s)
      Yasuda Takeshi、Kagawa Wataru、Tajima Katsushi
    • Journal Title

      PLOS Genetics

      Volume: 14 Issue: 3 Pages: 1007277-1007277

    • DOI

      10.1371/journal.pgen.1007277

    • NAID

      120006459820

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Impact of the SCF signaling pathway on leukemia stem cell-mediated ATL initiation and progression in an HBZ transgenic mouse model.2016

    • Author(s)
      Kuribayashi W, Takizawa K, Sugata K, Kuramitsu M, Momose H, Sasaki E, Hiradate Y, Furuhata K, Asada Y, Iwama A, Matsuoka M, Mizukami T*, Hamaguchi I*.
    • Journal Title

      Oncotarget

      Volume: 7(32) Issue: 32 Pages: 51027-51043

    • DOI

      10.18632/oncotarget.10210

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access

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Published: 2016-04-21   Modified: 2020-03-30  

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