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Repairing of heamatopoietic niche in bone marrow after X-ray irradiation

Research Project

Project/Area Number 16K09867
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionKeio University

Principal Investigator

Mise-Omata Setsuko  慶應義塾大学, 医学部(信濃町), 特任助教 (00269052)

Co-Investigator(Kenkyū-buntansha) 青木 和広  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (40272603)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords骨代謝 / 脂肪細胞 / 造血幹細胞ニッチ / マクロファージ / Spred / 造血幹細胞移植 / NF-kB / 骨芽細胞 / インフラマソーム / NF-kB / 免疫学 / 放射線 / 移植・再生医療
Outline of Final Research Achievements

Lethal X-ray radiation before HSC transplantation often induce the bone loss in the patients. We found a correlation between bone loss and the impairment of hematopoietic environment induced by hyper-differentiation of adipocytes, by using two different strains of mice, one is RelA-deficient mouse suffering from severe bone loss and the other is Spred1/Spred2 double knockout mouse which increases its bone mass after HSC transplantation. The adipocytes differentiated in the bone morrow after X-ray radiation were rapidly deprived in the Spred DKO mice and in these mice hematopoietic ability was enhanced compared with wild type mice. In contrast, the number of adipocytes markedly increased and hematopoietic ability was impaired in RelA-deficient mice. Inflammatory macrophages are highly differentiated in RelA-deficient mice, it may cause the over-differentiation of adipocytes.

Academic Significance and Societal Importance of the Research Achievements

造血幹細胞移植は、白血病や再生不良性貧血などで病気からの治癒を目指すことのできる唯一の治療法である。造血幹細胞移植を行う前には、患者自身の造血細胞を死滅させるために致死量のX線照射や抗がん剤投与などが行われるが、X線照射を受けた患者のなかには、骨量が減少し治療後のQOLが著しく低下するケースがある。本研究成果によってX線照射は脂肪細胞の分化を引き起こし、その分化が強いと骨形成や造血が低下し、その反対に脂肪細胞が少ないと骨形成や造血が亢進することを明らかにした。本研究成果は、造血幹細胞移植後の患者のQOLの向上に一助を与えるものと考える。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (10 results)

All 2019 2018 2017 2016

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 7 results) Presentation (2 results)

  • [Journal Article] Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery2019

    • Author(s)
      Ito Minako、Komai Kyoko、Mise-Omata Setsuko、Iizuka-Koga Mana、Noguchi Yoshiko、Kondo Taisuke、Sakai Ryota、Matsuo Kazuhiko、Nakayama Takashi、Yoshie Osamu、Nakatsukasa Hiroko、Chikuma Shunsuke、Shichita Takashi、Yoshimura Akihiko
    • Journal Title

      Nature

      Volume: 565 Issue: 7738 Pages: 246-250

    • DOI

      10.1038/s41586-018-0824-5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation and application of human induced-stem cell memory T cells for adoptive immunotherapy.2018

    • Author(s)
      Taisuke Kondo Yuki Imura Shunsuke Chikuma Sana Hibino Setsuko Omata‐Mise Makoto Ando Takashi Akanuma Mana Iizuka Ryota Sakai Rimpei Morita Akihiko Yoshimura
    • Journal Title

      Cancer Science

      Volume: 109 Issue: 7 Pages: 2130-2140

    • DOI

      10.1111/cas.13648

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of Nr4a receptors enhances anti-tumor immunity by breaking Treg-mediated immune tolerance.2018

    • Author(s)
      Hibino S, Chikuma S, Kondo T, Ito M, Nakatsukasa H, Omata-Mise S, Yoshimura A
    • Journal Title

      Cancer Res

      Volume: Epub Issue: 11 Pages: 3027-3040

    • DOI

      10.1158/0008-5472.can-17-3102

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of Nr4a receptors enhances anti-tumor immunity by breaking Treg-mediated immune tolerance2018

    • Author(s)
      Sana Hibino, Shunsuke Chikuma, Taisuke Kondo, Minako Ito, Hiroko Nakatsukasa, Setsuko Omata-Mise, and Akihiko Yoshimura,
    • Journal Title

      Cancer Research

      Volume: 印刷中

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Suppressors of cytokine signaling: Potential immune checkpoint molecules for cancer immunotherapy.2017

    • Author(s)
      Chikuma S, Kanamori M, Mise-Omata S, Yoshimura A.
    • Journal Title

      Cancer Sci

      Volume: 108 Issue: 4 Pages: 574-580

    • DOI

      10.1111/cas.13194

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Peptide drugs accelerate BMP-2-induced calvarial bone regeneration and stimulate osteoblast differentiation through mTORC1 signaling.2016

    • Author(s)
      Sugamori Y, Mise-Omata S, Maeda C, Aoki S, Tabata Y, Murali R, Yasuda H, Udagawa N, Suzuki H, Honma M, Aoki K.
    • Journal Title

      Bioessays

      Volume: 38 Issue: 8 Pages: 717-725

    • DOI

      10.1002/bies.201600104

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Peptide-induced de novo bone formation after tooth extraction prevents alveolar bone loss in a murine tooth extraction model.2016

    • Author(s)
      Arai Y, Aoki K, Shimizu Y, Tabata Y, Ono T, Murali R, Mise-Omata S, Wakabayashi N
    • Journal Title

      Eur J Pharmacol

      Volume: 782 Pages: 89-97

    • DOI

      10.1016/j.ejphar.2016.04.049

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Delivery of RANKL-Binding Peptide OP3-4 Promotes BMP-2-Induced Maxillary Bone Regeneration.2016

    • Author(s)
      Uehara T, Mise-Omata S, Matsui M, Tabata Y, Murali R, Miyashin M, Aoki K.
    • Journal Title

      J Dent Res.

      Volume: 95 Issue: 6 Pages: 665-672

    • DOI

      10.1177/0022034516633170

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Blockade of suppressor of cytokine signaling 3 enhances anti-tumor immunity2018

    • Author(s)
      Setsuko Mise-Omata and Akihiko Yoshimura
    • Organizer
      日本免疫学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 放射線照射後の骨髄内環境の修復における骨髄マクロファージの役割2016

    • Author(s)
      三瀬節子
    • Organizer
      第2回骨免疫学会
    • Place of Presentation
      ホテルモントレ沖縄スパ&リゾート(沖縄県恩納村)
    • Year and Date
      2016-07-06
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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