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In vivo generation of hematopoietic stem cells from human iPS cells in sheep fetal liver

Research Project

Project/Area Number 16K21315
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Hematology
Integrative animal science
Research InstitutionJichi Medical University

Principal Investigator

Abe Tomoyuki  自治医科大学, 医学部, 講師 (20610364)

Research Collaborator HANAZONO Yutaka  自治医科大学, 医学部, 教授 (70251246)
NAGAO Yoshikazu  宇都宮大学, 農学部, 教授 (70291953)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords造血幹細胞 / ニッチ / 多能性幹細胞 / 大型動物 / トランスレーショナルリサーチ / 再生医学 / 幹細胞 / 移植・再生医療 / 応用動物 / 血液内科学 / 再生医療 / 応用動物科学
Outline of Final Research Achievements

Generating hematopoietic stem cells (HSCs) from human iPSCs has been a great challenge. We hypothesized some key environmental factors are missing in vitro. Therefore, we tried in vivo generation of HSCs from human iPSCs. In this study, we generated human/sheep hematopoietic chimera; that is, sheep that have human HSCs derived from human iPSCs. Human iPSCs were cultured on murine stromal OP9 cells with multiple cytokines for 6 days for differentiation to a hematopoietic lineage. The cells were then transplanted into the liver of busulfan-conditioned fetal sheep. The engraftment of human hematopoietic cells was quantitatively evaluated by PCR of colony-forming units. Considering that many researchers have long failed to generate engraftable HSCs from human iPSCs, the data here imply that the acquisition of hematopoietic engraftment ability of human iPSCs may depend on the in vivo microenvironment such as in the fetal sheep liver. We are now taking out human HSCs from the sheep.

Report

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

    (7 results)

All 2017 2016 Other

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] CD34-negative hematopoietic stem cells show distinct expression profiles of homing molecules that limit engraftment in mice and sheep2017

    • Author(s)
      Abe Tomoyuki、Matsuoka Yoshikazu、Nagao Yoshikazu、Sonoda Yoshiaki、Hanazono Yutaka
    • Journal Title

      International Journal of Hematology

      Volume: 106 Issue: 5 Pages: 631-637

    • DOI

      10.1007/s12185-017-2290-5

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 異種移植系における同一ドナー由来リンパ球の影響2017

    • Author(s)
      阿部朋行、柴田宏昭、原弘真、魚崎英毅、大貫貴広、竹内絢香、原明日香、ボラジギン・サラントラガ、長尾慶和、花園豊
    • Organizer
      第20回日本異種移植研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Generation of CD45-positive Hematopoietic Cells from Human iPS Cells in Vivo in Ovine Fetal Liver2017

    • Author(s)
      Tomoyuki Abe, Hiroaki Shibata, Hideki Uosaki, Hiromasa Hara, Takahiro Ohnuki, Suvd Byambaa, Nawin Chanthra, Borjigin Sarentonglaga, Rika Fukumori, Yoshikazu Nagao, Yutaka Hanazono.
    • Organizer
      The International Society for Stem Cells Research 2017 Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [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
    • Related Report
      2017 Annual Research 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
      メルパルク京都4階(京都府京都市)
    • Related Report
      2016 Research-status Report
  • [Remarks] 自治医科大学 分子病態治療研究センター 再生医学研究部

    • URL

      http://www.jichi.ac.jp/saisei/

    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 造血系細胞の作製方法2016

    • 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
    • Filing Date
      2016-08-26
    • Related Report
      2016 Research-status Report
    • Overseas

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Published: 2016-04-21   Modified: 2019-03-29  

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