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Cancer stem cell assay by a new immunodeficient mouse model harboring a complete macrophage tolerance

Research Project

Project/Area Number 24659463
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Hematology
Research InstitutionKyushu University

Principal Investigator

AKASHI KOICHI  九州大学, 医学(系)研究科(研究院), 教授 (80380385)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsがん幹細胞 / 異種移植アッセイ / マクロファージ / SIRPA / 異種移植モデル / 免疫不全マウス / マクロファージ寛容 / CD47
Outline of Final Research Achievements

To evaluate human cancer stem cells in xenotransplant models, a variety of immunodeficient mouse lines have been developed. We found that in xenograft engraftment, inhibition of phagocytic reaction of mouse macrophages is essential in addition to lymphoid depletion. Murine signal regulatory protein alpha (mSIRPA) on macrophages cannot bind to human CD47 (hCD47), resulting phagocytic reaction against human cells. Here, we have established a new immunodeficient BRGhS mouse line, B6.Rag2(null)Il2rg(null), harboring a complete macrophage tolerance. BRGhS mouse line was introduced by human SIRPA, which allows to bind human CD47, resulting in inhibition of phagocytosis against human cell graft. BRGhS strain should be very useful in future xenotransplant experiments of human cancer stem cells.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (27 results)

All 2015 2014 2013 2012 Other

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Open Access: 1 results) Presentation (16 results) (of which Invited: 6 results)

  • [Journal Article] CD41 marks the initial myelo-erythroid lineage specification in adult mouse hematopoiesis: redefinition of murine common myeloid progenitor.2015

    • Author(s)
      Miyawaki K, Arinobu Y, Iwasaki H, Kohno K, Tsuzuki H, Iino T, Shima T, Kikushige Y, Takenaka K, Miyamoto T, Akashi K.
    • Journal Title

      Stem Cells

      Volume: 33 Issue: 3 Pages: 976-87

    • DOI

      10.1002/stem.1906

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The ordered acquisition of Class II and Class I mutations directs formation of human t(8;21) acute myelogenous leukemia stem cell.2014

    • Author(s)
      Shima T, Miyamoto T, Kikushige Y, Yuda J, Tochigi T, Yoshimoto G, Kato K, Takenaka K, Iwasaki H, Mizuno S, Goto N, Akashi K.
    • Journal Title

      Exp. Hematol.

      Volume: 42 Issue: 11 Pages: 955-65

    • DOI

      10.1016/j.exphem.2014.07.267

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The BALB/c-specific polymorphic SIRPA enhances its affinity for human CD47, inhibiting phagocytosis against human cells to promote xenogeneic engraftment.2014

    • Author(s)
      Iwamoto C
    • Journal Title

      Exp Hematol

      Volume: 42 Issue: 3 Pages: 163-171

    • DOI

      10.1016/j.exphem.2013.11.005

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Quantification of hematogones at the time of engraftment is a useful prognostic indicator in allogeneic stem cell transplantation.2013

    • Author(s)
      Shima T
    • Journal Title

      Blood

      Volume: 121 Issue: 5 Pages: 840-848

    • DOI

      10.1182/blood-2012-02-409607

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Successful treatment with anti-CC chemokine receptor 4 MoAb of relapsed adult T-cell leukemia/lymphoma after umbilical cord blood transplantation.2013

    • Author(s)
      Ito Y, Miyamoto T, Chong Y, Aoki T, Kato K, Akashi K, Kamimura T.
    • Journal Title

      Bone Marrow Transplant

      Volume: 48 Issue: 7 Pages: 998-999

    • DOI

      10.1038/bmt.2012.268

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Polymorphic Sirpa is the genetic determinant for NOD-based mouse lines to achieve efficient human cell engraftment.2013

    • Author(s)
      Yamauchi T
    • Journal Title

      Blood

      Volume: 121 Issue: 8 Pages: 1316-1325

    • DOI

      10.1182/blood-2012-06-440354

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Contribution of bone marrow-derived hematopoietic stem/progenitor cells to the generation of donor-marker(+) cardiomyocytes in vivo.2013

    • Author(s)
      Fukata M, Ishikawa F, Najima Y, Yamauchi T, Saito Y, Takenaka K, Miyawaki K, Shimazu H, Shimoda K, Kanemaru T, Nakamura K, Odashiro K, Nagafuji K, Harada M, Akashi K.
    • Journal Title

      PLoS One

      Volume: 8 Issue: 5 Pages: e62506-e62506

    • DOI

      10.1371/journal.pone.0062506

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reciprocal expression of enteric antimicrobial proteins in intestinal graft-versus-host disease.2013

    • Author(s)
      Eriguchi Y, Uryu H, Nakamura K, Shimoji S, Takashima S, Iwasaki H, Miyamoto T, Shimono N, Hashimoto D, Akashi K, Ayabe T, Teshima T.
    • Journal Title

      Biol Blood Marrow Transplant

      Volume: 19 Issue: 10 Pages: 1525-1529

    • DOI

      10.1016/j.bbmt.2013.07.027

    • NAID

      120005347004

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] TIM-3 as a therapeutic target for malignant stem cells in acute myelogenous leukemia2013

    • Author(s)
      Kikushige Y, Akashi K
    • Journal Title

      Ann NY Acad Sci

      Volume: 1266 Issue: 1 Pages: 118-123

    • DOI

      10.1111/j.1749-6632.2012.06550.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Monitoring of minimal residual disease (MRD) is useful to predict prognosis of adult patients with Ph-negative ALL : results of a prospective study (ALL MRD2002 Study)2013

    • Author(s)
      Nagafuji K, Miyamoto T, Eto T, Kamimura T, Taniguchi S, Okamura T, Ohtsuka E, Yoshida T, Higuchi M, Yoshimoto G, Fujisaki T, Abe Y, Takamatsu Y, Yokota S, Akashi K, Harada M. (16名, 6番目)
    • Journal Title

      J Hematol Oncol

      Volume: 6 Issue: 1 Pages: 14-14

    • DOI

      10.1186/1756-8722-6-14

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Engulfment of hematopoietic stem cel ls caused by down-regulation of CD47 is critical in the pathogenesis of hemophagocytic lymphohistiocytosis2012

    • Author(s)
      Kuriyama T, Takenaka K 他12名
    • Journal Title

      Blood

      Volume: 120巻 Issue: 19 Pages: 4058-4067

    • DOI

      10.1182/blood-2012-02-408864

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] TIM-3 Signaling and Human Myeloid Leukemia Stem Cell Development2015

    • Author(s)
      Koichi Akashi
    • Organizer
      KEYSTONE SYMPOSIA
    • Place of Presentation
      Keystone, Colorado, USA
    • Year and Date
      2015-02-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 白血病幹細胞研究のすゝめ2014

    • Author(s)
      赤司 浩一
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-11-02
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 造血器腫瘍幹細胞2014

    • Author(s)
      赤司 浩一
    • Organizer
      第101回近畿血液学地方会
    • Place of Presentation
      大阪
    • Year and Date
      2014-06-28
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] TIM-3, as a Target for Eradication of Cancer Stem Cells2014

    • Author(s)
      Koichi Akashi
    • Organizer
      The Uehara Memorial Foundation Symposium
    • Place of Presentation
      東京
    • Year and Date
      2014-06-17
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 造血器腫瘍幹細胞2014

    • Author(s)
      赤司 浩一
    • Organizer
      第3回日本血液学会東海地方会
    • Place of Presentation
      名古屋
    • Year and Date
      2014-04-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Cancer Stem Cell2014

    • Author(s)
      赤司 浩一
    • Organizer
      第87回日本内分泌学会学術総会
    • Place of Presentation
      福岡
    • Year and Date
      2014-04-24
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 造血幹細胞と造血器癌幹細胞

    • Author(s)
      赤司 浩一
    • Organizer
      第110回日本内科学会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Epigenetic Landscape of Hematopoietic Lineage Commitment Can Be Visualized by Analysis of Incorporated H3.3 Variant

    • Author(s)
      Koichi Akashi
    • Organizer
      ISEH 42nd Annual Scientific Meeting
    • Place of Presentation
      Vienna, Austria
    • Related Report
      2013 Research-status Report
  • [Presentation] Epigenetic landscape of hematopoiesis visualized by histone H3.3 incorporation is deregulated in acute myeloid leukemia

    • Author(s)
      Koichi Akashi
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Cancer Stem Cells in Human Hematological Malignancies

    • Author(s)
      Koichi Akashi
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Visualization of the epigenetic landscape of hematopoietic lineage commitment based on the analysis of histone H3.3 incorporation

    • Author(s)
      Koichi Akashi
    • Organizer
      第75回日本血液学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
  • [Presentation] 造血器癌幹細胞  Malignant hematopoietic stem cell

    • Author(s)
      赤司 浩一
    • Organizer
      第55回日本小児血液・がん学会学術集会
    • Place of Presentation
      福岡
    • Related Report
      2013 Research-status Report
  • [Presentation] 造血器悪性幹細胞の成立機構

    • Author(s)
      赤司 浩一
    • Organizer
      第101回日本病理学会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 慢性リンパ性白血病幹細胞の特性と治療応用

    • Author(s)
      赤司 浩一
    • Organizer
      第10回日本臨床腫瘍学会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
  • [Presentation] 悪性造血器腫瘍における癌幹細胞の病理

    • Author(s)
      赤司 浩一
    • Organizer
      第71回日本癌学会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] Transcription Factor Regulation of Normal and Malignant Hematopoiesis

    • Author(s)
      赤司 浩一
    • Organizer
      2013USA-Japan Science Conference
    • Place of Presentation
      Maui,Hawaii
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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