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Distribution and hematopoietic regulatory function of stromal cells in hematopoietic microenvironment

Research Project

Project/Area Number 18K06846
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48010:Anatomy-related
Research InstitutionNihon University

Principal Investigator

AIZAWA Shin  日本大学, 医学部, 教授 (30202443)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords細胞・組織 / 老化促進マウス / 骨髄ストローマ細胞 / 造血微小環境 / マクロファージ / 三次元骨髄培養 / サイトカイン / 細胞周期 / 三次元培養 / ストローマ細胞 / 老化促進モデルマウス
Outline of Final Research Achievements

The hematopoiesis is regulated by stromal cells, as distinguished from hematopoietic cells, in hematopoietic microenvironment. In this study, the stromal cells were shown as an essential compartment for regulating the proliferation and differentiation of hematopoietic cells by producing various cytokines and adhesion molecules. Furthermore, stromal cells protected the hematopoietic cells from biological stresses and keep the homeostasis of hematopoietic phenomena. These findings were verified by in vivo and in vitro examinations. The results showed the importance of stromal cells, especially macrophages, in hematopoietic microenvironment and the qualitative and quantitative impairment of stromal cells may result in the hematopoietic disorders.

Academic Significance and Societal Importance of the Research Achievements

本研究は造血を行ういわば「畑」である造血微小環境の構成要素としての「ストローマ細胞」に注目し、生体内(造血組織)における存在様式について、またこれら細胞が実際にどの様に造血幹細胞の増殖・分化に関わりを持って機能しているかをin vivo標本を用いて解析し、さらに新規に開発した三次元培養法を用いたin vitroの面からも検証したものである。これによりストローマ細胞による造血制御機構を解明し、「種」である造血細胞を育てるための「正しい畑を構築する」という観点から、今後人工骨髄の開発なども含めて白血病などの難治性造血器疾患に対する新規治療法の開発の可能性が示唆された研究である。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (9 results)

All 2021 2020 2019 2018

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (5 results)

  • [Journal Article] Abemaciclib induces atypical cell death in cancer cell characterized by formation of cytoplasmic vacuoles derived from lysosomes2020

    • Author(s)
      Hino Hirotsugu, Iriyama Noriyoshi, Kokuba Hiroko, Kazama Hiromi, Moriya Shota, Takano Naoharu, Hiramoto Masaki, Aizawa Shin, Miyazawa Keisuke
    • Journal Title

      Cancer Science

      Volume: - Issue: 6 Pages: 2132-2145

    • DOI

      10.1111/cas.14419

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dynamics of hematopoiesis is disrupted by impaired hematopoietic microenvironment in a mouse model of hemophagocytic lymphohistiocytosis2020

    • Author(s)
      Tsuboi Isao、Harada Tomonori、Hirabayashi Yoko、Aizawa Shin
    • Journal Title

      Annals of Hematology

      Volume: 99 Issue: 7 Pages: 1515-1523

    • DOI

      10.1007/s00277-020-04095-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Kinetics of leukemic cells in 3D culture with stromal cells and with arginine deprivation stress2020

    • Author(s)
      Harada T., Tsuboi I., Utsunomiya M., Yasuda M., Aizawa S.
    • Journal Title

      Journal of Bioscience and Bioengineering

      Volume: 130 Issue: 6 Pages: 650-658

    • DOI

      10.1016/j.jbiosc.2020.07.018

    • NAID

      40022441989

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Senescence-accelerated mice (SAMP1/TA-1) treated repeatedly with lipopolysaccharide develop a condition that resembles hemophagocytic lymphohistiocytosis2019

    • Author(s)
      Tsuboi Isao、Harada Tomonori、Hirabayashi Yoko、Aizawa Shin
    • Journal Title

      Haematologica

      Volume: 104 Issue: 10 Pages: 1995-2005

    • DOI

      10.3324/haematol.2018.209551

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Hematopoietic tissue is one of the organs that suffer lifethreatening damage in HLH2021

    • Author(s)
      原田智紀、壷井功、日野浩嗣、内藤美智子、原弘之、相澤信
    • Organizer
      第126回日本解剖学会総会・全国学術集会 / 第98回日本生理学会大会 合同大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] LPS投与による血球貪食性リンパ組織球症様病態像モデルマウス2020

    • Author(s)
      原田智紀、壷井功、日野浩嗣、内藤美智子、原弘之、相澤信
    • Organizer
      第125回日本解剖学会総会・全国学術集会
    • Related Report
      2020 Annual Research Report 2019 Research-status Report
  • [Presentation] LPS投与頻回により老化促進モデルマウス(SAMP1/TA-1)は血球貪食性リンパ組織球症様病態像を呈する2019

    • Author(s)
      原田智紀、壷井功、相澤信
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 造血制御システムの破綻と老化2019

    • Author(s)
      原田智紀、相澤信
    • Organizer
      第124回日本解剖学会総会全国学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Chemosennsitivity study in a model of simulated bone marrow: three-dimensional culture system2018

    • Author(s)
      Harada T, Tsuboi I., Aizawa S
    • Organizer
      第80回日本血液学会学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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