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Approaches to standardization of humanized mice by transplanting human hematopoietic stem cells (HSC) and thymus generated from induced pluripotent stem (iPS) cells.

Research Project

Project/Area Number 18H03975
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 42:Veterinary medical science, animal science, and related fields
Research InstitutionCentral Institute for Experimental Animals

Principal Investigator

ITO MAMORU  公益財団法人実験動物中央研究所, 役員, 所長 (00176364)

Co-Investigator(Kenkyū-buntansha) 伊藤 亮治  公益財団法人実験動物中央研究所, 実験動物応用研究部, 室長 (60425436)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥41,990,000 (Direct Cost: ¥32,300,000、Indirect Cost: ¥9,690,000)
Fiscal Year 2021: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Fiscal Year 2020: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2019: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
Fiscal Year 2018: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
KeywordsiPS細胞 / 造血幹細胞 / 胸腺 / ヒト化マウス / 免疫不全マウス / 分化 / IPS細胞 / iPS
Outline of Final Research Achievements

We conducted experiments to induce differentiation from human induced pluripotent stem cells (iPS) into human hematopoietic stem cells and human thymus. During the four-year study period, we investigated various differentiation conditions for human hematopoietic stem cells and human thymus, and transplanted them into immunodeficient mice. However, human hematopoietic cells could not be detected even by transplantation of hematopoietic stem like cells differentiated from iPS. It did not reach the originally planned standardization of humanized mice.
On the other hand, the newly developed NOG-c-kitV831M (W41) mouse was found to be an immunodeficient mouse extremely useful as a recipient for human hematopoietic stem cell transplantation. That is, hematopoietic stem cell transplantation into NOG-W41 mice can engraft even a very small number of cells without X-ray irradiation compared to NOG mice, and human hematopoietic cells engrafted in NOG-W41 mice can be engrafted in NOG mice.

Academic Significance and Societal Importance of the Research Achievements

ヒト疾患やその治療の研究、検証のためには、ヒトの細胞や組織を持つヒトマウスは極めて有用である。このヒト化マウスの標準化のために、ヒトiPS細胞よりヒト造血幹細胞やヒト胸腺上皮細胞への分化の検討を行った。この4年間で十分な結果は出せなかったが、今後とも重要なテーなである。一方でヒト化マウス作製のための新しい免疫不全マウスを作出できた。このマウスを使うことで少数の造血幹細胞でヒト化マウスができるようになれば、より安価にヒト化マウスを使うことができるようになる。

Report

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

    (2 results)

All 2019 2017

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

  • [Journal Article] Humanized mouse models: Application to human diseases2017

    • Author(s)
      Ito Ryoji、Takahashi Takeshi、Ito Mamoru
    • Journal Title

      J Cell Physiol.

      Volume: 233 Issue: 5 Pages: 3723-3728

    • DOI

      10.1002/jcp.26045

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Book] NOGマウス2019

    • Author(s)
      伊藤守
    • Total Pages
      4
    • Publisher
      公益社団法人日本実験動物協会 Labio 21
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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