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Characterization of human CD34-negative hematopoietic stem cells and their differentiation pathway and hierarchy

Research Project

Project/Area Number 24591432
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionKansai Medical University

Principal Investigator

SONODA YOSHIAKI  関西医科大学, 医学部, 教授 (60206688)

Co-Investigator(Renkei-kenkyūsha) SASAKI Yutaka  関西医科大学, 医学部, 准教授 (80425066)
MATSUOKA Yoshikazu  関西医科大学, 医学部, 助教 (70533420)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords造血幹細胞 / 臍帯血 / CD34抗原 / CD133抗原 / 骨髄内移植 / SCID-repopulating cell / 階層制 / 臍帯血移植 / HSC / SRC / CD34 / CD133 / MSC / hierarchy / cord blood / HSCT / IBMI / MPL
Outline of Final Research Achievements

We have identified human cord blood-derived very primitive CD34-negative hematopoietic stem cell (CD34-HSC) using the intra-bone marrow injection method for the first time. Recently, we developed a high resolution purification method for CD34-HSC using 18 lineage specific antibodies and succeeded to identify CD133 antigen as a specific positive marker for CD34+/- HSCs. Furthermore, we performed a variety of in vitro and in vivo experiments to clarify the human HSC hierarchy. These data demonstrated that our identified CD34-HSC seemed to be more immature than the CD34+CD38-HSC whidh was previously thought as the most primitive human HSC.
Based on these data, we propose that the myeloid-biased long-term repopulating CD34-HSCs reside in the apex of human HSC hierarchy.

Report

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

    (46 results)

All 2015 2014 2013 2012 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (36 results) (of which Invited: 10 results) Book (4 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Prospectively isolated human bone marrow cell-derived MSCs support primitive human CD34-negative hematopoietic stem cells2015

    • Author(s)
      Matsuoka Y, Nakatsuka R, Sumide K, Kawamura H, Takahashi M, Fujioka T, Uemura Y, Asano H, Sasaki Y, Inoue M, Ogawa H, Takahashi T, Hino M, Sonoda Y
    • Journal Title

      Stem Cells

      Volume: 33 Issue: 5 Pages: 1554-1565

    • DOI

      10.1002/stem.1941

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Human cord blood-derived primitive CD34-negative hematopoietic stem cells (HSCs) are myeloid-biased long-term repopulating HSCs2015

    • Author(s)
      Matsuoka Y, Sumide K, Kawamura H, Nakatsuka R, Fujioka T, Sasaki Y, Sonoda Y
    • Journal Title

      Blood Cancer Journal

      Volume: -

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Mouse dental pulp stem cells support human umbilical cord blood-derived hematopoietic stem/progenitor cells in vitro2015

    • Author(s)
      Nakatsuka R, Matsuoka Y, Uemura Y, Sumide K, Iwaki R, Takahashi M, Fujioka T, Sasaki Y, Sonoda Y
    • Journal Title

      Cell Transplantation

      Volume: (印刷中) Issue: 1 Pages: 97-113

    • DOI

      10.3727/096368913x674675

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD133 is a positive marker for a distinct class of primitive human cord blood-derived CD34-negative hematopoietic stem cells.2014

    • Author(s)
      Takahashi M et al.
    • Journal Title

      Leukemia.

      Volume: 28 Issue: 6 Pages: 1308-15

    • DOI

      10.1038/leu.2013.326

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ヒト造血幹細胞支持能を有するヒト骨髄間葉系幹細胞の予期的分離とその機能解析2015

    • Author(s)
      松岡由和、角出啓輔、河村 猛、中塚隆介、藤岡龍也、佐々木豊、薗田精昭
    • Organizer
      第14回日本再生医療学会総会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] CD133抗原を用いる移植用臍帯血の造血幹細胞活性評価法の開発2015

    • Author(s)
      松岡由和、高橋雅也、角出啓輔、中塚隆介、藤岡龍也、佐々木豊、薗田精昭
    • Organizer
      第37回日本造血細胞移植学会総会
    • Place of Presentation
      神戸国際会議場(神戸)
    • Year and Date
      2015-03-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] ヒト造血幹細胞ーその特性はどこまで解明されたのかー2015

    • Author(s)
      薗田精昭
    • Organizer
      第37回日本造血細胞移植学会総会
    • Place of Presentation
      神戸国際会議場(神戸)
    • Year and Date
      2015-03-06
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] CD133 is a positive marker of human cord blood-derived CD34-negative hematopoietic stem cells2014

    • Author(s)
      Takahashi M, Matsuoka Y, Sumide K, Nakatsuka R, Fujioka T, Sasaki Y, Kaneko K, Sonoda Y
    • Organizer
      The 76th Annual Meeting of the Japanese Society of Hematology
    • Place of Presentation
      Osaka International Convention Center, Osaka
    • Year and Date
      2014-11-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] Cord blood-derived CD34-negative hematopoietic stem cell (HSC) is myeloid-biased HSC residing at the apex of the human HSC hierarchy.2014

    • Author(s)
      Matsuoka Y, Sumide K, Takahashi M, Nakatsuka R, Fujioka T, Sasaki Y, Sonoda Y
    • Organizer
      The 76th Annual Meeting of the Japanese Society of Hematology
    • Place of Presentation
      Osaka International Convention Center, Osaka
    • Year and Date
      2014-10-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] ヒト造血幹細胞の純化と階層制の解明2014

    • Author(s)
      薗田精昭
    • Organizer
      第24回日本サイトメトリー学会総会
    • Place of Presentation
      関西医科大学(枚方市)
    • Year and Date
      2014-06-29
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 未分化ヒト臍帯血由来CD34抗原陰性造血幹細胞は骨髄球系細胞への分化指向性を有する2014

    • Author(s)
      松岡由和、角出啓輔、高橋雅也、中塚隆介、藤岡龍也、佐々木豊、薗田精昭
    • Organizer
      第24回日本サイトメトリー学会総会
    • Place of Presentation
      関西医科大学(枚方市)
    • Year and Date
      2014-06-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] ヒト臍帯血由来未分化造血幹細胞におけるMPL発現の機能的意義2014

    • Author(s)
      松岡由和、角出啓輔、高橋雅也、中塚隆介、藤岡龍也、佐々木豊、薗田精昭
    • Organizer
      第24回日本サイトメトリー学会総会
    • Place of Presentation
      関西医科大学(枚方市)
    • Year and Date
      2014-06-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] CD133はヒト臍帯血由来CD34抗原陰性未分化造血幹細胞の陽性マーカーである2014

    • Author(s)
      高橋雅也、松岡由和、角出啓輔、中塚隆介、藤岡龍也、佐々木豊、金子一成、薗田精昭
    • Organizer
      第24回日本サイトメトリー学会総会
    • Place of Presentation
      関西医科大学(枚方市)
    • Year and Date
      2014-06-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] ヒト造血幹細胞の純化と階層制の解明2014

    • Author(s)
      薗田精昭
    • Organizer
      第2回奈良県輸血・造血細胞治療研究会
    • Place of Presentation
      奈良県新公会堂(奈良市)
    • Year and Date
      2014-06-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] CD133 is a positive marker of human cord blood-derived CD34-negative hematopoietic stem cells2014

    • Author(s)
      Takahashi M, Matsuoka Y, Sumide K, Nakatsuka R, Fujioka T, Sasaki Y, Kaneko K, Sonoda Y
    • Organizer
      The 12th Stem Cell Research Symposium
    • Place of Presentation
      Centennial Hall Kyushu University School of Medicine, Fukuoka
    • Year and Date
      2014-05-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] Cord blood-derived CD34-negative hematopoietic stem cells (HSCs) are myeloid-biased HSCs residing at the apex of the human HSC hierarchy.2014

    • Author(s)
      Matsuoka Y, Sumide K, Takahashi M, Nakatsuka R, Fujioka T, Sasaki Y, Sonoda Y
    • Organizer
      The 12th Stem Cell Research Symposium
    • Place of Presentation
      Centennial Hall Kyushu University School of Medicine, Fukuoka
    • Year and Date
      2014-05-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] CD133抗原はCD34+/-SCID-repopulating cellの陽性マーカーである2014

    • Author(s)
      高橋雅也、松岡由和、角出啓輔、中塚隆介、藤岡龍也、佐々木豊、薗田精昭
    • Organizer
      第22回近畿臍帯血幹細胞移植研究会
    • Place of Presentation
      ホテルグランビア大阪(大阪市)
    • Year and Date
      2014-05-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] Biochemical analysis of human CD34+/-HSC-supporting mechanisms by human bone marrow-derived mesenchymal stromal cells.2012

    • Author(s)
      Matsuoka Y, Sasaki Y, Takahashi M, Iwaki R, Nakatsuka R, Kohno H, Fujioka T, Sonoda Y.
    • Organizer
      The 10th Stem Cell Research Symposium
    • Place of Presentation
      淡路夢舞台(淡路市)
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒト臍帯血由来CD34抗原陽性及び陰性造血幹/前駆細胞は異なる分化能を有する

    • Author(s)
      松岡由和、高橋雅也、岩城隆二、角出啓輔、中塚隆介、藤岡龍也、佐々木豊、薗田精昭
    • Organizer
      第21回近畿臍帯血幹細胞移植研究会
    • Place of Presentation
      グランヴィア大阪(大阪市)
    • Related Report
      2013 Research-status Report
  • [Presentation] Functional significance of MPL expression in the primitive human hematopoietic stem cell compartment

    • Author(s)
      Takahashi M, Matsuoka Y, Nakatsuka R, Iwaki R, Kohno H, Fujioka T, Sasaki Y, Sonoda Y
    • Organizer
      The 11th Stem Cell Research Symposium
    • Place of Presentation
      The University of Tokyo, Ito International Research Center (Tokyo)
    • Related Report
      2013 Research-status Report
  • [Presentation] Functional significance of MPL expression in the human primitive hematopoietic stem cell compartment

    • Author(s)
      Sonoda Y
    • Organizer
      1st Conference of Polish Society of Regenerative Medicine
    • Place of Presentation
      Szczecin (Poland)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] ヒト造血幹細胞支持能を有するヒト骨髄由来間葉系幹細胞の予期的分離とその機能解析

    • Author(s)
      松岡由和、薗田精昭
    • Organizer
      第23回日本サイトメトリー学会
    • Place of Presentation
      日本医科大学 橘桜会館(東京都)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] A revised model of human hematopoietic stem cell hierarchy

    • Author(s)
      Sonoda Y
    • Organizer
      The Soeul National University Seminar
    • Place of Presentation
      Seoul National University (Korea)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] A revised model of human hematopoietic stem cell hierarchy

    • Author(s)
      Sonoda Y
    • Organizer
      Asan Stem Cell Symposium 2013: New Horizons of Stem Cell Therapeutics
    • Place of Presentation
      University of Ulsan College of Medicine (Korea)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] ヒト造血幹細胞の新しい階層制モデルの提唱

    • Author(s)
      薗田 精昭
    • Organizer
      第4回癌・免疫若手セミナー
    • Place of Presentation
      関西医科大学(枚方市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Functional significance of MPL expression in the primitive human hematopoietic stem cell compartment

    • Author(s)
      Takahashi M, Matsuoka Y, Nakatsuka R, Sumide K, Iwaki R, Fujioka T, Sasaki Y, Sonoda Y
    • Organizer
      The 75th Annual Meeting of the Japanese Society of Hematology
    • Place of Presentation
      さっぽろ芸文館(札幌市)
    • Related Report
      2013 Research-status Report
  • [Presentation] CD133 is a positive marker of human cord blood-derived CD34-negative hematopoietic stem cells.

    • Author(s)
      Takahashi M, Matsuoka Y, Sumida K, Nakatsuka R, Fujioka T, Kohno H, Sasaki Y, Matsui K, Asano H, Kaneko K, Sonoda Y
    • Organizer
      The 55th Annual Meeting and Exposition of American Society of Hematology
    • Place of Presentation
      New Orleans (USA)
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒト臍帯血由来未分化造血幹細胞におけるMPL発現の機能的意義

    • Author(s)
      高橋雅也、松岡由和、角出啓輔、中塚隆介、藤岡龍也、佐々木豊、薗田精昭
    • Organizer
      第36回日本造血細胞移植学会総会
    • Place of Presentation
      ラグナガーデンホテル(那覇)
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒト造血幹細胞のhierarchyに関する新しいモデルの提唱

    • Author(s)
      薗田精昭
    • Organizer
      第1回Kagawa Basic Research Forum
    • Place of Presentation
      高松商工会議所(高松市)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] マウス歯髄幹細胞によるヒト臍帯血由来未分化造血幹細胞支持能の解析

    • Author(s)
      中塚隆介、松岡由和、高橋雅也、岩城隆二、藤岡龍哉、佐々木豊、薗田精昭
    • Organizer
      第20回近畿臍帯血幹細胞移植研究会
    • Place of Presentation
      ホテルグランビア大阪(大阪市)
    • Related Report
      2012 Research-status Report
  • [Presentation] Prospectively isolated PDGFRA and Sca-1 double positive dental pulp-derived mesenchymal stem cell-like cells have different characteristics as compared to PDGFRA and Sca-1 double positive bone marrow-derived mesenchymal stem cells.

    • Author(s)
      Nakatsuka R, Uemura Y, Matsuoka Y, Takahashi M, Iwaki R, Fujioka T, Sasaki Y, Sonoda Y.
    • Organizer
      The 10th Annual Meeting of the International Society for Stem Cell Research
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Related Report
      2012 Research-status Report
  • [Presentation] Novel human bone marrow derived mesenchymal stromal cells lacking adipogenic differentiation potential support primitive human CD34-negative hematopoietic stem cells.

    • Author(s)
      Matsuoka Y, Sasaki Y, Takahashi M, Iwaki R, Nakatsuka R, Kohno H, Fujioka T, Uemura Y, Asano H, Sonoda Y.
    • Organizer
      The 10th Annual Meeting of the International Society for Stem Cell Research
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Related Report
      2012 Research-status Report
  • [Presentation] マウス歯髄幹細胞と骨髄間葉系幹細胞の機能比較とヒト造血幹細胞のin vitro支持能の検討

    • Author(s)
      中塚隆介、松岡由和、高橋雅也、岩城隆二、藤岡龍哉、植村靖史、佐々木豊、薗田精昭
    • Organizer
      第22回日本サイトメトリー学会総会
    • Place of Presentation
      千里ライフサイエンスセンター(豊中市)
    • Related Report
      2012 Research-status Report
  • [Presentation] FACSにより予期的に分離されたマウスSca-1, PDGFRa陽性歯髄幹細胞は同一の表面免疫特性を持つ骨髄由来間葉系幹細胞とは異なる幹細胞特性を有する

    • Author(s)
      中塚隆介、植村靖史、薗田精昭
    • Organizer
      第54回歯科基礎学会
    • Place of Presentation
      奥羽大学(郡山市)
    • Related Report
      2012 Research-status Report
  • [Presentation] Human CD34-negative hematopoietic stem cells express potent erythroid/megakaryocytic potential.

    • Author(s)
      Matsuoka Y, Takahashi M, Sasaki Y, Iwaki R, Nakatsuka R, Fujioka T, Kohno H, Sonoda Y.
    • Organizer
      The 74th Annual Meeting of the Japanese Society of Hematology
    • Place of Presentation
      国立京都国際会館(京都市)
    • Related Report
      2012 Research-status Report
  • [Presentation] Functional significance of MPL expression in the human primitive hematopoietic stem cell compartment.

    • Author(s)
      Takahashi M, Matsuoka Y, Iwaki R, Nakatsuka R, Fujioka T, Kohno H, Matsui K, Asano H, Sasaki Y, Kaneko K, Sonoda Y.
    • Organizer
      The 54th Annual Meeting of the American Society of Hematology
    • Place of Presentation
      Atlanta (USA)
    • Related Report
      2012 Research-status Report
  • [Presentation] Development of a highly efficient method for isolating very small embryonic-like stem cells identified in adult mouse and human bone and their stem cell characteristics.

    • Author(s)
      Sonoda Y.
    • Organizer
      James Graham Brown Cancer Center Stem Cell Conference
    • Place of Presentation
      Louisville (USA)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] ヒト臍帯血由来CD34抗原陰性造血幹/前駆細胞は高い巨核球/赤血球分化能を有する

    • Author(s)
      松岡由和、高橋雅也、岩城隆二、中塚隆介、藤岡龍哉、佐々木豊、薗田精昭
    • Organizer
      第35回日本造血細胞移植学会総会
    • Place of Presentation
      ANAクラウンプラザホテル(金沢市)
    • Related Report
      2012 Research-status Report
  • [Presentation] マウス切歯由来Sca-1,PDGFRa陽性間葉系幹細胞のヒト臍帯血由来造血幹細胞支持能について

    • Author(s)
      中塚隆介、松岡由和、高橋雅也、岩城隆二、藤岡龍哉、佐々木豊、薗田精昭
    • Organizer
      第35回日本造血細胞移植学会総会
    • Place of Presentation
      ANAクラウンプラザホテル(金沢市)
    • Related Report
      2012 Research-status Report
  • [Presentation] Functional significance of MPL expression in the human primitive hematopoietic stem cell compartment.

    • Author(s)
      Takahashi M, Matsuoka Y, Nakatsuka R, Iwaki R, Kohno H, Fujioka T, Sasaki Y, Sonoda Y.
    • Organizer
      The 11th Stem Cell Research Symposium
    • Place of Presentation
      Ito International Research Center (Tokyo)
    • Related Report
      2012 Research-status Report
  • [Book] 造血器腫瘍アトラス 改訂第5版2015

    • Author(s)
      薗田精昭
    • Total Pages
      600
    • Publisher
      日本医事新報社
    • Related Report
      2014 Annual Research Report
  • [Book] 臍帯血移植の基礎と臨床2014

    • Author(s)
      薗田精昭
    • Total Pages
      273
    • Publisher
      医学書院
    • Related Report
      2014 Annual Research Report
  • [Book] Adult Stem Cell Therapies: Alternatives to Plasticity2014

    • Author(s)
      Sonoda Y
    • Total Pages
      263
    • Publisher
      Humana Press, Springer
    • Related Report
      2014 Annual Research Report
  • [Book] 臍帯血移植の基礎と臨床2013

    • Author(s)
      薗田精昭
    • Total Pages
      250
    • Publisher
      医学書院
    • Related Report
      2012 Research-status Report
  • [Remarks] 関西医科大学衛生学講座

    • URL

      http://www3.kmu.ac.jp/hygiene/

    • Related Report
      2013 Research-status Report
  • [Patent(Industrial Property Rights)] ヒト造血幹細胞濃縮画分の製造方法2014

    • Inventor(s)
      薗田精昭、松岡由和、角出啓輔
    • Industrial Property Rights Holder
      薗田精昭、松岡由和、角出啓輔
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-04-24
    • Related Report
      2013 Research-status Report

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

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