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Placental/Umbilical cord blood-derived mesenchymal stem cell-likestroma cells support the hematopoietic recovery of X-irradiated human CD34+ cells

Research Project

Project/Area Number 18390327
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionHirosaki University

Principal Investigator

KASHIWAKURA Ikuo  Hirosaki University, 大学院・保健学研究科, 教授 (00177370)

Co-Investigator(Kenkyū-buntansha) 高橋 賢次  弘前大学, 大学院・保健学研究科, 助教 (00400143)
阿部 由直  弘前大学, 大学院・医学研究科, 教授 (10167950)
稲波 修  北海道大学, 獣医学研究科, 教授 (10193559)
Co-Investigator(Renkei-kenkyūsha) 稲波 修  北海道大学, 獣医学研究科, 教授 (10193559)
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥8,860,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2008: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2007: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywords間葉系幹細胞 / 造血幹細胞 / 造血前駆細胞 / 放射線 / 臍帯血
Research Abstract

放射線非照射及び照射CD34陽性細胞(ヒト造血幹・前駆細胞)を、臍帯血由来間葉系幹細胞様ストローマ細胞と共培養することにより、サイトカイン単独での培養に比べ有意に高い細胞増殖及び未分化維持といった造血支持能が示された。サイトカインを共培養開始16 時間後に添加すると、照射細胞はストローマ非存在下培養では著しく造血が低下したが、共培養では同時添加した場合と同等の造血が認められた。この時、共培養上清中のヒアルロン酸は顕著に増加し、一方硫酸化グリコサミノグリカンはストローマ非存在下放射線照射細胞単独培養で有意に増加した。同様に幾つかのサイトカイン産生も放射線照射細胞単独培養で増加した。以上の結果から、間葉系幹細胞様ストローマ細胞は放射線曝露ヒト造血幹・前駆細胞の造血再生に有用であることが明らかとなった。この時、造血幹/前駆細胞とストローマ細胞との接触刺激が重要であると共に、細胞外マトリックス成分産生が大きく関与している可能性が示唆された。また、本研究の関連成果が2 件の特許出願に繋がった。

Report

(4 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (48 results)

All 2009 2008 2007 2006 Other

All Journal Article (26 results) (of which Peer Reviewed: 20 results) Presentation (16 results) Remarks (3 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Placental/umbilical cordblood-derived mesenchymal stem cell-likestroma cells support the hematopoieticrecovery of X-irradiated human CD34^+ cells2009

    • Author(s)
      N. Hayashi, K. Takahashi, Y. Abe and I. Kashiwakura
    • Journal Title

      Life Sciences 84(17-18)

      Pages: 598-605

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of radiation-induced apoptosis of human lymphoma U937 cells by sanazole2009

    • Author(s)
      D.Y. Yu, Q.L. Zhao, Z.L. Wei, T. Nomura, I. Kashiwakura, T.V. Kagiya, T. Kondo
    • Journal Title

      Apoptosis 4

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Placental/Umbilical cord blood-derived mesenchymal stemcell-like stroma cells support the hematopoietic recovery of X-irradiated human CD34^+ cells2009

    • Author(s)
      N. Hayashi, et.al.
    • Journal Title

      Life Sciences 84

      Pages: 598-605

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of radiation-induced apoptosis of human lymphoma U937 cells by sanazole2009

    • Author(s)
      D-Y. Yu, et.al.
    • Journal Title

      Apoptosis (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of a 2-step culture with cytokinecombinations on megakaryocytopoiesis andthrombopoiesis from carbon-ion beamirradiatedhuman hematopoietic stem/progenitor cells2008

    • Author(s)
      K. Takahashi, S. Monzen, H. Yoshino, Y.Abe, K. Eguchi-Kasai and I. Kashiwakura
    • Journal Title

      J Radiat Res 49(4)

      Pages: 417-424

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential induction fromX-irradiated human peripheral blood monocytes to dendritic cells2008

    • Author(s)
      H. Yoshino, K. Takahashi, S. Monzen, I.Kashiwakura
    • Journal Title

      J Radiat Res,(Tokyo) 49(3)

      Pages: 293-303

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of HIF-1α by theanticancer drug TAS106 enhances X-rayinducedapoptosis in vitro and in vivo2008

    • Author(s)
      H. Yasui, A. Ogura, T. Asanuma, A. Matsuda, I. Kashiwakura, M. Kuwabara, and O. Inanami
    • Journal Title

      BritJ Cancer 99(9)

      Pages: 1442-52

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Takagaki. Ex vivoexpansions of megakaryocytopoiesis fromplacental and umbilical cord blood CD34^+cells in serum-free culture supplementedwith proteoglycans extracted from the nasalcartilage of salmon heads and the nasal septum cartelage of whale2008

    • Author(s)
      I. Kashiwakura, K. Takahashi, S. Monzen, T. Nakamura and K. Takagaki
    • Journal Title

      Life Sciences 82(19-20)

      Pages: 1023-1031

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Individual differences in theradiosensitivity of hematopoietic progenitorcells detected in steady-state humanperipheral blood2008

    • Author(s)
      A. Oriya, K. Takahashi, O. Inanami, T.Miura, Y. Abe, M. Kuwabara, I.Kashiwakura
    • Journal Title

      J Radiat Res (Tokyo) 49(2)

      Pages: 113-121

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Individual differences in the radiosensitivity of hematopoietic progenitor cells detectedin steady-state human peripheral blood2008

    • Author(s)
      A. Oriya, et. al.,
    • Journal Title

      Journal of Radiation Research 49

      Pages: 113-121

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ex vivo expansions of megakaryocytopoiesis from placental and umbilical cord blood CD34^+ cells in serum-free culture supplemented with proteoglycans extracted from the nasal cartilage of salmon heads and the nasal septum cartelage of whale2008

    • Author(s)
      I. Kashiwakura, et. al.,
    • Journal Title

      Life Sciences (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential induction from X-irradiated human peripheral blood monocytes to dendritic cells2008

    • Author(s)
      H. Yoshino, et. al.,
    • Journal Title

      Journal of Radiation Research (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of a 2-step culture with cytokine combinations on megakaryocytopoiesis and thrombopoiesis from carbon-ion beam-irradiated human hematopoietic stem/progenitor cells2008

    • Author(s)
      K. Takahashi, et. al.,
    • Journal Title

      Journal of Radiation Research (in press)

    • NAID

      130007001303

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Severe damageby heavy ion beam-irradiation on humanmegakaryocytopoiesis and thrombopoiesis2007

    • Author(s)
      K. Takahashi, S. Monzen, K. Eguchi-Kasai, Y. Abe and I. Kashiwakura
    • Journal Title

      Radiat Res 168(5)

      Pages: 545-551

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Takagaki. Application of proteoglycanextracted from the nasal cartilage of salmonheads for ex vivo expansion ofhematopoietic progenitor cells derived from human placental/umbilical cord blood2007

    • Author(s)
      I. Kashiwakura, K. Takahashi and K. Takagaki
    • Journal Title

      Glycoconj J 24(4-5)

      Pages: 251-258

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Kuwabara. Purvalanol A enhances cellkilling by inhibiting up-regulation of CDC2kinase activity in tumor cells irradiated with high doses of X rays2007

    • Author(s)
      D. Iizuka, O. Inanami, I. Kashiwakura and M. Kuwabara
    • Journal Title

      Radiat Res 167(5)

      Pages: 563-571

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Severe damage by heavy ion beam-irradiation on human megakaryocytopoiesis and thrombopoiesis2007

    • Author(s)
      K. Takahashi, et. al.,
    • Journal Title

      Radiation Research 168

      Pages: 545-551

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sensitization of radiation-induced cell killing by inhibiting Cdc2 kinase activity with purvalanol A.2007

    • Author(s)
      D.Iizuka, et al.
    • Journal Title

      Radiation Research (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Application of proteoglycan extracted from the nasal cartilage of salmon heads for ex vivo expansion of hematopoietic progenitor cells derived from human placental/umbilical cord blood.2007

    • Author(s)
      I.Kashiwakura, et al.
    • Journal Title

      Glycoconjugate Journal (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The effects of (-)-epigallocatechin-3-gallateon the proliferation and differentiation ofhuman megakaryocytic progenitor cells2006

    • Author(s)
      S. Monzen, T. Mori, K. Takahashi, Y. Abe, O. Inanami, M. Kuwabara and I. Kashiwakura
    • Journal Title

      Jradiat Res, (Tokyo) 47(2)

      Pages: 213-220

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Takahashi, M. Kuwabara.Regenerative induction of megakaryopoiesisand thrombopoiesis in vitro fromX-irradiated CD34^+ cells prepared fromhuman placental and umbilical cord blood2006

    • Author(s)
      I. Kashiwakura, O. Inanami, Y. Abe, K.Satoh, T. A.
    • Journal Title

      Radiat Res 166(2)

      Pages: 345-351

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Takahashi and K. Takagaki. Theeffects of glycosaminoglycans on thrombopoietin-induced megakaryocytopoiesis2006

    • Author(s)
      I. Kashiwakura, T. Teramachi, I. Kakizaki, Y. Takagi, T.A. Takahashi and K. Takagaki
    • Journal Title

      Haematologica 91(4)

      Pages: 445-451

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Glycosaminoglycans potentiate human megakaryocytopoiesis induced by thrombopoietin.2006

    • Author(s)
      I.Kashiwakura, et al.
    • Journal Title

      Haematologica 91・4

      Pages: 445-451

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Regenerative induction of megakaryopoiesis and thrombopoiesis in vitro from X-irradiated CD34^+ cells prepared from human placental and umbilical cord blood.2006

    • Author(s)
      I.Kashiwakura, et al.
    • Journal Title

      Radiation Research 166・2

      Pages: 345-351

    • NAID

      110004772466

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The effects of (-)-epigallocatechin-3-gallate on the proliferation and differentiation of human megakaryocytic progenitor cells.2006

    • Author(s)
      S.Monzen, et al.
    • Journal Title

      Journal of Radiation Research 47・2

      Pages: 213-210

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The effects of heavy ion particles on human megakaryocytopoiesis and thrombopoiesis.2006

    • Author(s)
      I.Kashiwakura, et al.
    • Journal Title

      Blood 108

      Pages: 4156-4156

    • Related Report
      2006 Annual Research Report
  • [Presentation] 放射線曝露ヒトCD34^+細胞の造血回復に対する臍帯血由来間葉系幹細胞の関与2008

    • Author(s)
      林直樹, 他
    • Organizer
      日本放射線影響学会第51回大会
    • Place of Presentation
      北九州市
    • Year and Date
      2008-11-20
    • Related Report
      2008 Annual Research Report
  • [Presentation] 放射線曝露ヒト造血幹細胞の造血回復に及ぼす臍帯血由来間葉系幹細胞様ストローマの関与2008

    • Author(s)
      林直樹, 他
    • Organizer
      第2回東北糖鎖研究会
    • Place of Presentation
      弘前市
    • Year and Date
      2008-09-26
    • Related Report
      2008 Annual Research Report
  • [Presentation] ヒトCD34 陽性細胞の分化および遺伝子発現に強定常磁場が及ぼす作用2008

    • Author(s)
      門前暁, 高橋賢次, 土岐力, 伊藤悦朗, 櫻井智徳, 宮越順二, 柏倉幾郎
    • Organizer
      第47 回日本医学放射線学会生物部会学術大会
    • Place of Presentation
      ホテル日航高知旭ロイヤル, 高知市
    • Year and Date
      2008-06-21
    • Related Report
      2008 Final Research Report
  • [Presentation] Eguchi-Kasai. Effects ofhigh LET-radiation on humanmegakaryocytopoiesis and thrombopoiesis2008

    • Author(s)
      K. Takahashi, I. Kashiwakura, S. Monzen, H.Yoshino, Y. Abe, K
    • Organizer
      (ISEH 37^<th> Annual ScientificMeeting, Boston
    • Place of Presentation
      MA, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] ヒト末梢血単球由来樹状細胞の分化誘導における放射線の影響2008

    • Author(s)
      吉野浩教, 高橋賢次, 柏倉幾郎
    • Organizer
      日本放射線影響学会第51回大会
    • Place of Presentation
      北九州国際会議場, 北九州市
    • Related Report
      2008 Final Research Report
  • [Presentation] 放射線曝露ヒトCD34+細胞の造血回復に対する臍帯血由来間葉系幹細胞の関与2008

    • Author(s)
      林直樹, 高橋賢次, 柏倉幾郎
    • Organizer
      日本放射線影日本放射線影響学会第51回大会
    • Place of Presentation
      北九州国際会議場, 北九州市
    • Related Report
      2008 Final Research Report
  • [Presentation] ヒト末梢血造血前駆細胞の増殖及び誘導好中球の機能に対する放射線の影響とrhG-CSF の作用2008

    • Author(s)
      勝盛健雄, 林雅子, 高橋賢次, 柏倉幾郎
    • Organizer
      日本放射線影響学会第51回大会
    • Place of Presentation
      北九州国際会議場, 北九州市
    • Related Report
      2008 Final Research Report
  • [Presentation] ヒト末梢血造血前駆細胞の放射線感受性におけるNrf2 の応答2008

    • Author(s)
      加藤健吾, 高橋賢次, 門前暁, 丸山淳史, 伊東健, 柏倉幾郎
    • Organizer
      日本放射線影響学会第51回大会
    • Place of Presentation
      北九州国際会議場, 北九州市
    • Related Report
      2008 Final Research Report
  • [Presentation] 放射線曝露ヒト造血幹細胞の造血回復に及ぼす臍帯血由来間葉系幹細胞様ストローマの関与2008

    • Author(s)
      林直樹, 門前暁, 吉野浩教, 高橋賢次, 中村敏也, 阿部由直, 柏倉幾郎
    • Organizer
      第2 回東北糖鎖研究会
    • Place of Presentation
      弘前大学医学部コミュニケーションセンター
    • Related Report
      2008 Final Research Report
  • [Presentation] 間葉系幹細胞の造血支持能を利用した放射線曝露造血幹細胞からの造血再生2007

    • Author(s)
      林直樹、高橋賢次、柏倉幾郎
    • Place of Presentation
      千葉市幕張メッセ
    • Year and Date
      2007-11-16
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] サイトカイン複合培養による重粒子線曝露造血幹/前駆細胞からの巨核球・血小板産生の回復2007

    • Author(s)
      高橋賢次、柏倉幾郎
    • Organizer
      日本放射線影響学会第50回大会
    • Place of Presentation
      千葉市幕張メッセ
    • Year and Date
      2007-11-16
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] ヒトCD34陽性細胞におけるTie2の発現と放射線感受性2007

    • Author(s)
      門前暁、高橋賢次、阿部由直、柏倉幾郎
    • Organizer
      第46回日本医学放射線学会生物部会学術大会
    • Place of Presentation
      つくば国際会議場
    • Year and Date
      2007-07-21
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] Tie-2-expression controls the radiosensitivityof hematopoietic stem/progenitorcells2007

    • Author(s)
      K. Takahashi, S. Monzen, I. Kashiwakura
    • Organizer
      49^<th> Annual Meeting and Exposition of American Society of Hematology
    • Place of Presentation
      Atlanta,GA, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] Differential Induction from X-irradiatedHuman Peripheral Blood Monocytes toDentritic Cells2007

    • Author(s)
      H. Yoshino, K. Takahashi I. Kashiwakura
    • Organizer
      13^<th> International Congress of Radiation Research
    • Place of Presentation
      San Francisco, CA,USA
    • Related Report
      2008 Final Research Report
  • [Presentation] The effects ofheavy ion particles on human megakaryocytopoiesisand thrombopoiesis2006

    • Author(s)
      I. Kashiwakura, K. Takahashi, S. Monzen, K.Eguchi-Kasai, T. Toki, Y. Abe
    • Organizer
      48^<th> Annual Meeting and Exposition of American Societyof Hematology
    • Place of Presentation
      Orland, FL, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] Takagaki. The effects of glycosaminoglycanson thrombopoietin-inducedmegakaryocytopoiesis2006

    • Author(s)
      K. Takahashi, I. Kashiwakura, T. Toki, K
    • Organizer
      48^<th> Annual Meetingand Exposition of American Society of Hematology
    • Place of Presentation
      Orland, FL, USA
    • Related Report
      2008 Final Research Report
  • [Remarks]

    • URL

      http://www.hs.hirosaki-u.ac.jp/~kashiwakura/

    • Related Report
      2008 Final Research Report
  • [Remarks]

    • URL

      http://www.hs.hirosaki-u.ac.jp/~kashiwakura/home.html

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.hs.hirosaki-u.ac.jp/~kashiwakura/

    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] 遺伝子発現の制御方法および造血幹細胞の分化・増幅方法2007

    • Inventor(s)
      柏倉幾郎、宮越順二、高橋賢次、櫻井智徳、門前 暁
    • Industrial Property Rights Holder
      弘前大学
    • Industrial Property Number
      2007-238584
    • Filing Date
      2007-09-13
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Patent(Industrial Property Rights)] ヒト細胞の培養培地および培養方法2007

    • Inventor(s)
      柏倉幾郎、高橋賢次
    • Industrial Property Rights Holder
      弘前大学
    • Industrial Property Number
      2007-089829
    • Filing Date
      2007-03-29
    • Related Report
      2008 Final Research Report
  • [Patent(Industrial Property Rights)] ヒト細胞の培養培地および培養方法2007

    • Inventor(s)
      柏倉幾郎, 高橋賢次
    • Industrial Property Rights Holder
      弘前大学
    • Industrial Property Number
      2007-089829
    • Filing Date
      2007-03-29
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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