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A fetal development using an interspecies surrogate mother

Research Project

Project/Area Number 18K14602
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 42030:Animal life science-related
Research InstitutionNational Institute for Physiological Sciences (2021)
The University of Tokyo (2018-2020)

Principal Investigator

Nishimura Toshiya  生理学研究所, 行動・代謝分子解析センター, 特別訪問研究員 (00803842)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords幹細胞 / 発生学 / 臓器再生 / 獣医 / イヌ / 子宮 / キメラ / 細胞競合ニッチ / 異種 / 臓器作製 / 個体発生 / 胚盤胞補完法
Outline of Final Research Achievements

In this study, we proceeded with the research for the purpose of establishing a novel fetal development system using an interspecies surrogate mother, and as a result, we succeeded to produce two strains of genetically modified rats with Dach1 and Dach2 gene defects, respectively. We also revealed that the functions of these genes differs between mice and rats in terms of uterine development. Furthermore, we developed a method (termed cell competition niche method) that dramatically increases donor chimerism in chimeric animals and posted it in a well-known international journal. Furthermore, based on this result, a patent application was filed in the United States, and an international patent is currently being applied for. In addition, the results obtained in this research were presented at three international conferences, one domestic conference, and one invited lecture.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、これまで作製出来ていなかったDach1,2遺伝子変異を有した遺伝子改変ラットを作製しその機能を明らかにするものであり、その学術的意義は高い。また、本研究にて開発した手法は、世界的に研究が進められてきた動物体内でドナー幹細胞由来の臓器を作製する研究において、これまで問題とされていた低いドナーキメリズムの問題を解決するものであり、本分野を飛躍的に進歩させる可能性を有している。さらに、本成果を通してヒト幹細胞由来臓器を作製することができれば、移植治療における慢性的な臓器不足を解決する画期的な手法となり得ることからその社会的意義は高い。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (10 results)

All 2021 2020 2019 2018

All Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 2 results) Presentation (5 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Journal Article] Generation of Functional Organs Using a Cell-Competitive Niche in Intra- and Inter-species Rodent Chimeras2021

    • Author(s)
      Nishimura Toshiya、Suchy Fabian P.、Bhadury Joydeep、Igarashi Kyomi J.、Charlesworth Carsten T.、Nakauchi Hiromitsu
    • Journal Title

      Cell Stem Cell

      Volume: 28 Issue: 1 Pages: 141-149.e3

    • DOI

      10.1016/j.stem.2020.11.019

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Streamlined and quantitative detection of chimerism in mouse tissue using digital PCR2020

    • Author(s)
      Suchy Fabian P.、Nishimura Toshiya、Wilkinson Adam C.、Higuchi Maimi、Bhadury Joydeep、Nakauchi Hiromitsu
    • Journal Title

      bioRxiv

      Volume: online

    • DOI

      10.1101/2020.11.04.368944

    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Journal Article] Generation of Footprint-Free Canine Induced Pluripotent Stem Cells Using Auto-Erasable Sendai Virus Vector2018

    • Author(s)
      Tsukamoto Masaya、Nishimura Toshiya、Yodoe Kyohei、Kanegi Ryoji、Tsujimoto Yasunori、Alam Md Emtiaj、Kuramochi Mizuki、Kuwamura Mitsuru、Ohtaka Manami、Nishimura Ken、Nakanishi Mahito、Inaba Toshio、Sugiura Kikuya、Hatoya Shingo
    • Journal Title

      Stem Cells and Development

      Volume: 27 Issue: 22 Pages: 1577-1586

    • DOI

      10.1089/scd.2018.0084

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] IGF1R DELETION IN A HOST EMBRYO AUGMENTS DONOR CONTIBUTION TO HOST TISSUES IN BOTH INTRA- AND INTER-RODENT CHIMERAS2021

    • Author(s)
      Toshiya Nishimura, Fabian Suchy, Joydeep bhadury, Kyomi Igarashi, Carsten Charlesworth, Hiromitsu Nakauchi
    • Organizer
      ISSCR 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DONOR CELLS PREDOMINANTLY PROLIFERATE IN IGF1R KNOCKOUT RODENT EMBRYOS2021

    • Author(s)
      Toshiya Nishimura, Fabian Suchy, Joydeep bhadury, Kyomi Igarashi, Carsten Charlesworth, Hiromitsu Nakauchi
    • Organizer
      ISSCR/JSRM International Symposium Virtual
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] キメラ技術による腎臓再生の最前線2021

    • Author(s)
      西村俊哉
    • Organizer
      第164回日本獣医学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 細胞競合ニッチ法を用いた幹細胞由臓器の誘導2021

    • Author(s)
      西村 俊哉, Fabian Suchy, Joydeep Bhadury, 五十嵐経美 ,Carsten Charlesworth, 中内啓光
    • Organizer
      第20回日本再生医療学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Blastocyst Injection Rescues The postnatal Growth Retardation In Chimeric Mouse2019

    • Author(s)
      T. Nishimura, J. Bhadury, F. P. Suchy, C. Charlesworth, H. Nakauchi
    • Organizer
      ASCB EMBO 2019 meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] PRODUCTION OF HUMAN CELLS, TISSUES, AND ORGANS IN A GROWTH FACTOR RECEPTOR-DEFICIENT ANIMAL HOST2021

    • Inventor(s)
      Toshiya Nishimura、他2名
    • Industrial Property Rights Holder
      Stanford University, 東京大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] PRODUCTION OF HUMAN CELLS, TISSUES, AND ORGANS IN A GROWTH FACTOR RECEPTOR-DEFICIENT ANIMAL HOST2020

    • Inventor(s)
      Toshiya Nishimura
    • Industrial Property Rights Holder
      Toshiya Nishimura
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report
    • Overseas

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Published: 2018-04-23   Modified: 2024-12-25  

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