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inAnalyses of stem cells niche in ovine fetus liver for hematopoietic differntiation of human iPS cells in

Research Project

Project/Area Number 26501002
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Regenerative medicine
Research InstitutionUtsunomiya University

Principal Investigator

NAGAO YOSHIKAZU  宇都宮大学, 農学部, 教授 (70291953)

Co-Investigator(Kenkyū-buntansha) 福森 理加  宇都宮大学, 農学部, 助教 (60721694)
Co-Investigator(Renkei-kenkyūsha) HANAZONO Yutaka  自治医科大学, 医学部, 教授 (70251246)
Research Collaborator ABE Tomoyuki  自治医科大学, 医学部, 講師 (20610364)
Project Period (FY) 2014-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
KeywordsiPS細胞 / 分化誘導 / 造血幹細胞 / ヒツジ胎子 / iPS / 再生医学 / 大動物 / ヒツジ / 再生医学・医療 / ヒトiPS細胞 / 胎子 / 再生医学・医療 / 幹細胞
Outline of Final Research Achievements

Hematopoietic engraftment has been shown to observe when early differentiated monkey ES cells were transplanted into fetal liver. In this study, we examined optimal condition of ovine fetal liver for hematopoietic differentiation of the human iPS cells. We found that human hematopoietic chimera sheep can be efficiently generated when mesodermal early differentiated human iPS cells were injected into ovine fetal liver at 50-60 days of gestation. The human hematopoietic tissue was observed in ovine bone marrow for at least 4 years.

Academic Significance and Societal Importance of the Research Achievements

ESないしiPS細胞のin vitro分化誘導に関する研究が盛んに行われているが、造血幹細胞への分化誘導系はほとんど報告されていない。現在、薬剤で治療効果が少ない白血病に対しては、免疫が適合するドナーの骨髄中の造血幹細移植胞移植によって賄われており、本人のiPS細胞を活用した再生医療への期待が非常に高い。本研究は、患者本人のiPS細胞を、ヒツジ胎子肝内微小環境を用いて造血系へ分化誘導し、患者への移植に用いる白血病治療の可能性を明らかにした。また、ヒツジ胎子肝内の造血幹細胞誘導因子の解明が進めば、iPS細胞のin vitro造血系分化誘導への道も開けるだろう。

Report

(4 results)
  • 2018 Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (8 results)

All 2017 2016 2015 2014

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (5 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] A long-term follow-up study on the engraftment of human hematopoietic stem cells in sheep.2014

    • Author(s)
      Tomoyuki Abe, Yutaka Hanazono, Yoshikazu Nagao
    • Journal Title

      Experimental Animals

      Volume: 63 Issue: 99999 Pages: 475-481

    • DOI

      10.1538/expanim.63.475

    • NAID

      130004701642

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ヒトiPS細胞由来造血細胞のヒツジ体内での長期生着2017

    • Author(s)
      阿部朋行、柴田宏昭、魚崎英毅、原弘真、大貫貴広、スブド・ビャンバー、ナーウィン・ジャントラー、ボラジギン・サラントラガ、福森理加、長尾慶和、花園豊
    • Organizer
      第64回日本実験動物学会総会
    • Place of Presentation
      福島県郡山市
    • Year and Date
      2017-05-25
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒトiPS細胞由来造血細胞のヒツジ体内での長期生着2017

    • Author(s)
      阿部朋行、柴田宏昭、魚崎英毅、原弘真、大貫貴広、ボラジギン・サラントラガ、福森理加、長尾慶和、花園豊
    • Organizer
      第19回日本異種移植研究会
    • Place of Presentation
      京都府京都市
    • Year and Date
      2017-02-25
    • Related Report
      2016 Research-status Report
  • [Presentation] Factors affecting hematopoietic engraftment of monkey embryonic stem cells in sheep fetuses2015

    • Author(s)
      Yoshikazu Nagao, Tomoyuki Abe, Asuka Hara, Kazuko Ogata, Mio Yamaguchi, Borjigin Sarentonglaga, Rika Fukumori, Yutaka Hanazono.
    • Organizer
      The 41th Annual Conference of the International Embryo Transfer Society
    • Place of Presentation
      Versailles, France
    • Year and Date
      2015-01-10 – 2015-01-15
    • Related Report
      2014 Research-status Report
  • [Presentation] Pharmacodynamics of Remifentanil for fetus in the pregnant ewe2014

    • Author(s)
      Masaki Sato, Kenichi Masui, Nanako Mizuta, Yasuhiro Kogure, Yoshikazu Nagao, Hiroyuki Sumikura
    • Organizer
      Annual meeting of American Society of Anesthesiologists
    • Place of Presentation
      New Orleans, Louisiana, USA
    • Year and Date
      2014-10-11 – 2014-10-15
    • Related Report
      2014 Research-status Report
  • [Presentation] ヒツジ子宮内移植系におけるヒト造血細胞の生着・増幅技術の開発2014

    • Author(s)
      阿部朋行、長尾慶和、柳瀬公秀、原明日香、ボラジギン・サラントラガ、緒方和子、山口美緒、花園豊
    • Organizer
      第61回日本実験動物学会
    • Place of Presentation
      札幌市
    • Year and Date
      2014-05-15 – 2014-05-17
    • Related Report
      2014 Research-status Report
  • [Patent(Industrial Property Rights)] 造血系細胞の作出方法2016

    • Inventor(s)
      花園豊、阿部朋行、長尾慶和
    • Industrial Property Rights Holder
      花園豊、阿部朋行、長尾慶和
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-08-26
    • Related Report
      2016 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] 造血系細胞の作製方法2015

    • Inventor(s)
      花園豊、阿部朋行、長尾慶和
    • Industrial Property Rights Holder
      自治医科大学、宇都宮大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-168702
    • Filing Date
      2015-08-28
    • Related Report
      2015 Research-status Report

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Published: 2014-04-04   Modified: 2025-01-30  

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