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Clarification of the mechanism of differentiation from hematopoietic stem cell-derived cells to hepatic stellate cells

Research Project

Project/Area Number 20591150
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionMie University

Principal Investigator

MASUYA Masahiro  Mie University, 大学院・医学系研究科, 准教授 (30281083)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords単球 / 分化 / 肝星細胞 / MCP-1 / CCR2 / 肝線維化 / 造血細胞 / CCR2 antagonist / 四塩化炭素 / 骨髄単球系前駆細胞 / 肝傷害モデル
Research Abstract

We previously clarified that hematopoietic stem cell-derived cells were abele to differentiate into hepatic stellate cells (HpSCs) during carbon tetrachloride (CCl_4)-induced iver injury. Which lineage of cells are true precursors of HpSCs remains unknown. We idoptively transferred neutrophils, monocytes, eosinophils, B cells, or T cells, which were isolated rom enhanced green fluorescent protein (EGFP)-transgenic mice, into CCl_4-injured non-transgenic nice. In the livers of mice given monocytes, EGFP^+ HpSCs were detected. This suggest that a proportion of monocytes are precursors of HpSCs. Monocyte chemoattractant protein-1 (MCP-1) is bought to be associated with the invasion of monocytes into injured liver. CCR2, a receptor for vICP-1, is expressed on monocytes. We examined the effect of CCR2 antagonist against the lifferentiation of monocytes into HpSCs and found that the antagonist suppressed the number of EGFP^+ HpSCs and the area of fibrosis in injured liver.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (42 results)

All 2010 2009 2008

All Journal Article (23 results) (of which Peer Reviewed: 23 results) Presentation (19 results)

  • [Journal Article] Thrombocytopenia in mice lacking the carboxy-termainal regulatory domain of the Ets transcription factor Flil2010

    • Author(s)
      Moussa O, LaRue AC, Abangan RS Jr, Williams CR, Zhang XK, Masuya M, Gong YZ, Spyropoulos DD, Ogawa M, Gilkeson G, Watson DK
    • Journal Title

      Mol Cell Biol Vol.30, No.21

      Pages: 5194-5206

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] An efficient method for single hematopoietic stein cell engraftment in mice based on cell-cycle dormancy of hematopoietic stem cells2010

    • Author(s)
      Abe T, Masuya M, Ogawa M
    • Journal Title

      Exp Hematil Vol.38, No.7

      Pages: 603-608

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Drug interaction between itraconazole and bortezomib : exacerbation of peripheral neuropathy and thrombocytopenia induced by bortezomib2010

    • Author(s)
      Iwamoto T, Ishibashi M, Fujieda A, Masuya M, Katayama N, Okuda M
    • Journal Title

      Pharmacotherapy Vol.30, No.7

      Pages: 661-665

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Diagnostic value of PCR analysis of bacteria and fungi from blood in empiric-therapy-resistant febrile neutropenia2010

    • Author(s)
      Nakamura A, Sugimoto Y, Ohishi K, Sugawara Y, Fujieda A, Monma F, Suzuki K, Masuya M, Nakase K, Matsushima Y, Wada H, Katayama N, Nobori T
    • Journal Title

      J Clin Microbiol Vol.48, No.6

      Pages: 2030-2036

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A potential activity of valproic acid in the stimulation of interleukin-3-mediated megakaryopoiesis and erythropoiesis2010

    • Author(s)
      Liu B, Ohishi K, Yamamura K, Suzuki K, Monma F, Ino K, Nishii K, Masuya M, Sekine T, Heike Y, Takaue Y, Katayama N
    • Journal Title

      Exp Hematol Vol.38, No.8

      Pages: 685-695

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effect of washing solution on platelet counts following transfusion with twice-washed platelets : a single-patient experience2010

    • Author(s)
      Tanaka Y, Ohishi K, Yonekawa T, Yodoya N, Iwamoto S, Nishioka Y, Tatara Y, Matsumoto T, Masuya M
    • Journal Title

      Transfusion Med Vol.20, No.5

      Pages: 358-360

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] High-intensity signals in the basal ganglia from gadolinium-enhanced T1-weighted MRI as an early change in toxoplasma encephalitis in an AIDS patient2010

    • Author(s)
      Suzuki K, Masuya M, Matsumoto T, Ito N, Ohishi K, Maeda M, Katayama N
    • Journal Title

      J Infect Chemother Vol.16, No.2

      Pages: 135-138

    • NAID

      10027189643

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 同種末梢血幹細胞移植後長期間無再発生存中のアグレッシブNK細胞白血病2010

    • Author(s)
      伊野和子、桝屋正浩、中森良樹、鈴木圭、水谷実、関根隆夫、山口素子、中瀬一則、海田勝二、小川啓恭、片山直之
    • Journal Title

      臨床血液 51巻、4号

      Pages: 258-263

    • NAID

      10026332516

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Thrombocytopenia in mice lacking the carboxy-terminal regulatory domain of the Ets transcription factor Flil2010

    • Author(s)
      Moussa O, LaRue AC, et al.
    • Journal Title

      Mol Cell Biol.

      Volume: 30 Pages: 5192-5206

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An efficient method for single hematopoietic stem cell engraftment in mice based on cell-cycle dormancy of hematopoietic stem cells2010

    • Author(s)
      Abe T, Masuya M, Ogawa M
    • Journal Title

      Exp Hematol.

      Volume: 38 Pages: 603-608

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A potential activity of valproic acid in the stimulation of interleukin-3-mediated megakaryopoiesis and erythropoiesis2010

    • Author(s)
      Liu B, Ohishi K, et al.
    • Journal Title

      Exp Hematol.

      Volume: 38 Pages: 685-695

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Drug interaction between itraconazole and bortezomib : exacerbation of peripheral neuropathy and thrombocytopenia induced by bortezomib2010

    • Author(s)
      Iwamoto T, Ishibashi M, et al.
    • Journal Title

      Pharmacotherapy

      Volume: 30 Pages: 661-665

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of washing solution on platelet counts following transfusion with twice-washed platelets : a single-patient experience2010

    • Author(s)
      Tanaka Y, Ohishi K, et al.
    • Journal Title

      Transfus Med.

      Volume: 20 Pages: 358-360

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diagnostic value of PCR analysis of bacteria and fungi from blood in empiric-therapy-resistant febrile neutropenia2010

    • Author(s)
      Nakamura A, Sugimoto Y, et al.
    • Journal Title

      J Clin Microbiol.

      Volume: 48 Pages: 2030-2036

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High-intensity signals in the basal ganglia from gadolinium-enhanced T1-weighted MRI as an early change in toxoplasma encephalitis in an AIDS patient2010

    • Author(s)
      Suzuki K, Masuya M, et al.
    • Journal Title

      J Infect Chemother.

      Volume: 16 Pages: 135-138

    • NAID

      10027189643

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The effectiveness of measuring for fragmented red cells using an automated hematology analyzer in patients with thrombotic microangiopathy2009

    • Author(s)
      Abe Y, Wada H, Yamada E, Noda M, Ikejiri M, NIshioka J, Kobayashi T, Matsumoto T, Masuya M, Isaji S, Usui M, Uemoto S, Katayama N, Nobori T
    • Journal Title

      Clin Appl Thromb Hemost Vol.15, No.2

      Pages: 257-262

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 同種骨髄非破壊的移植後に形質細胞腫で再発・増悪した多発性骨髄腫3例の報告2009

    • Author(s)
      杉本由香, 西井一浩, 宮田恵里, 藤枝敦史, 山口素子, 桝屋正浩, 片山直之
    • Journal Title

      臨床血液 50

      Pages: 289-294

    • NAID

      10024959650

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The effectiveness of measuring for fragmented red cells using an automated hematology analyzer in patients with thrombotic microangiopathy2009

    • Author(s)
      Abe Y, Wada H, Yamada E, Noda M, Ikejiri M, Nishioka J, Kobayashi T, Matsumoto T, Masuya M, Isaji S, Usui M, Uemoto S, Katayama N, Nobori T
    • Journal Title

      Clin Appl Thromb Hemost 15

      Pages: 257-262

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual topology of functional Toll-like receptor 3 expression in human hepatocellular carcinoma2008

    • Author(s)
      Yoneda K, Sugimoto K, Shiraki K, Tanaka J, Beppu T, Fuke H, Yamamoto N, Masuya M, Horie R, Uchida K, Takei Y
    • Journal Title

      differential signaling mechanisms of TLR3-induced NF-kappaB activation and apoptosis Vol.33, No.5

      Pages: 929-936

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Deletion of chromosome arm 15q in a case of minimally differentiated hypoplastic AML-M02008

    • Author(s)
      Fujieda A, Masuya M, Kitano S, Miyazaki K, Yazaki A, Sugimoto Y, Usui E, Miyata E, Shibasaki T, Yamamura K, Ohishi K, Nishii K, Nakase K, Takeuchi Tm, Katayama N
    • Journal Title

      Cancer Genet Cytogenet Vol.184, No.1

      Pages: 57-61

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] ADAMTSI3 related markers and von Willebrand factor in plasma from patients with thrombotic microangiopathy (TMA)2008

    • Author(s)
      Kobayashi T, Wada H, Nishioka J, Yamamoto M, Matsumoto T, Tamara T, Nomura S, Masuya M, Mori Y, Nakatani K, Nishikawa M, Katayama N, Nobori T
    • Journal Title

      Thromb Res Vol.121, No.6

      Pages: 849-854

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dual topology of functional Toll-like receptor 3 expression inhuman hepatocellular carcinoma : differential signaling mechanisms of TLR3-induced NF-kappaB activation and apoptosis.2008

    • Author(s)
      Yoneda K, Sugimoto K, Shiraki K, Tanaka J, Beppu T, Fuke H, Yamamoto N, Masuya M, Horie R, Uchida K, Takei Y.
    • Journal Title

      Int J Oncol. 33

      Pages: 929-936

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deletion of chromosome arm 15q in a case of minimally differentiated hypoplastic AML-MO.2008

    • Author(s)
      Fujieda A, Masuya M. Kitano S, Miyazaki K, Yazaki A, Sugimoto Y, Usui E, Miyata E, Shibasaki T, Yamamura K, Ohishi K, Nishii K, Nakase K, Takeuchi T, Katayama N.
    • Journal Title

      Cancer Genet Cytogenet. 184

      Pages: 57-61

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Important role for flt3 Ligand in the generation of early B and T cell precursors from human primitive hematopoietic progenitors, revealed by telomerized human stromal cells2010

    • Author(s)
      Liu B, Ohishi K, Masuya M, Hamada H, Katayama N
    • Organizer
      52nd American Society of Hematology Meeting
    • Place of Presentation
      Orland, FL, USA (Poster)
    • Year and Date
      2010-12-05
    • Related Report
      2010 Final Research Report
  • [Presentation] Important role for flt3 Ligand in the generation of early B and T precursors from human primitive hematopoietic progenitors, revealed by telomerized human stromal cells.2010

    • Author(s)
      Lin B, Ohishi K, Masuya M, et al.
    • Organizer
      54th American Society of Hematology Annual Meeting
    • Place of Presentation
      Orlando, FL, USA
    • Year and Date
      2010-12-05
    • Related Report
      2010 Annual Research Report
  • [Presentation] Hematopoietic origin of pancreatic stellate cells2010

    • Author(s)
      伊野和子、桝屋正浩、宮田恵里、大有晃嗣、片山直之
    • Organizer
      第72回日本血液学会学術集会
    • Place of Presentation
      横浜、口演
    • Year and Date
      2010-09-24
    • Related Report
      2010 Final Research Report
  • [Presentation] Hematopoietic origin of pancreatic stellate cells2010

    • Author(s)
      伊野和子、桝屋正浩、宮田恵里, 他
    • Organizer
      第72回日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] Ly6C^+ inflammatory monocytes are extrahepatic precursors of hepatic stellate cells in liver injury2009

    • Author(s)
      Masahiro Masuya, Hiroto Araki, Kohshi Ohishi, Naoyuki Katayama
    • Organizer
      The 51^<st> Annual Meeting of American Society of Hematology
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2009-12-06
    • Related Report
      2009 Annual Research Report
  • [Presentation] Monocytic origin of hepatic stellate cells in liver injury2009

    • Author(s)
      Masuya M, Nakamura S, Miyata E, Araki H, Ohishi K, Katayama N
    • Organizer
      第71回日本血液学会学術総会
    • Place of Presentation
      京都 国立京都国際会議場
    • Year and Date
      2009-10-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] MLL-ENL融合遺伝子による形質転換は造血幹細胞のみを標的として生じる2009

    • Author(s)
      小埜良一, 桝屋正浩, 宮田恵里, 中島秀明, 上迫努, 伊藤守, 鈴木圭, 片山直之, 北村俊雄, 野坂哲哉
    • Organizer
      第68回日本癌学会総会
    • Place of Presentation
      横浜 パシフィコ横浜
    • Year and Date
      2009-10-01
    • Related Report
      2009 Annual Research Report
  • [Presentation] Ly6C^+ inflammatory monocytes are extrahepatic precursors of hepatic stellate cells in liver injury2009

    • Author(s)
      Masuya M, Araki H, Ohishi K, Katayama N
    • Organizer
      51th Annual Meeting of American Society of Hematology
    • Place of Presentation
      New Orleans, USA (Poster)
    • Related Report
      2010 Final Research Report
  • [Presentation] Evaluation of potential role for valproic acid in IL-3-mediated megakaryopoiesis and erythropoiesis in serum-free and serum-containing cultures2009

    • Author(s)
      Ohishi K, Liu B, Masuya M,, Heike Y, Takaue Y, Katayama N
    • Organizer
      51th Annual Meeting of American Society of Hematology
    • Place of Presentation
      New Orleans, LA, USA (Poster)
    • Related Report
      2010 Final Research Report
  • [Presentation] Transfusion of platelet concentrates washed twice with M-sol provided adequatepost-transfusion platelet count increments in an anhaptoglobinemic patient with anti-haptoglobin antibody2009

    • Author(s)
      Tanaka Y, Kassai C, Abe K, Nishio M, Maruyama M, Kamada N, Matsumoto T, Masuya M, Nishioka Y, Tatara Y, Ohishi K
    • Organizer
      The XXth Regional Congress of the International Society Blood Transfusion (ISBT) Asia
    • Place of Presentation
      Nagoya, Japan (Poster)
    • Related Report
      2010 Final Research Report
  • [Presentation] Valproic acid, in combination with IL-3, stimulates human megakaryopoiesis as well as erythropoiesis2009

    • Author(s)
      Ryuu H, Ohishi K, Masuya M, Heike Y, Takaue Y, Katayama N
    • Organizer
      第71回日本血液学会
    • Place of Presentation
      京都、口演
    • Related Report
      2010 Final Research Report
  • [Presentation] Ly6C+単球は肝傷害時の肝星細胞の前駆細胞である2009

    • Author(s)
      桝屋正浩、大石晃嗣、片山直之
    • Organizer
      第68回日本癌学会総会
    • Place of Presentation
      横浜、ポスター
    • Related Report
      2010 Final Research Report
  • [Presentation] MLL-ENL融合遺伝子による形質転換は造血幹細胞のみを標的として生じる2009

    • Author(s)
      小埜良一、桝屋正浩、宮田恵里、中島秀明、上迫努、伊藤守、鈴木圭、片山直之、北村俊雄、野坂哲哉
    • Organizer
      第68回日本癌学会総会
    • Place of Presentation
      横浜、口演
    • Related Report
      2010 Final Research Report
  • [Presentation] 肝線維化における肝星細胞は骨髄系造血細胞に由来する2008

    • Author(s)
      宮田恵里, 桝屋正浩, 片山直之
    • Organizer
      キリン血液疾患セミナー
    • Place of Presentation
      京都
    • Year and Date
      2008-11-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] 肝星細胞の起源の解明2008

    • Author(s)
      宮田恵里, 桝屋正浩, 片山直之
    • Organizer
      第4回騏麟塾
    • Place of Presentation
      東京(品川)
    • Year and Date
      2008-07-19
    • Related Report
      2008 Annual Research Report
  • [Presentation] IFN-αはPI3Kを介して造血前駆細胞のβ1インテグリンによる細胞接着を増強する2008

    • Author(s)
      桝屋正浩、大石晃嗣、中村志帆、宮田恵里、杉本由香、藤枝敦史、片山直之
    • Organizer
      第70回日本血液学会総会
    • Place of Presentation
      京都、ポスター
    • Related Report
      2010 Final Research Report
  • [Presentation] 血液疾患患者における末梢血細菌・真菌PCR検査の有用性の検討2008

    • Author(s)
      杉本由香、中村明子、大石晃嗣、宮田恵里、門間文彦、田丸智巳、藤枝敦史、山口素子、西井一浩、桝屋正浩、中瀬一則、松島佳子、和田英夫、登勉、片山直之
    • Organizer
      第70回日本血液学会総会
    • Place of Presentation
      京都、口演
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒト巨核球系前駆細胞の分化・増殖におけるヒストン脱アセチル化酵素の役割2008

    • Author(s)
      大有晃嗣、山村賢太郎、桝屋正浩、平家勇司、高上洋一、片山直之
    • Organizer
      第70回日本血液学会総会
    • Place of Presentation
      京都、口演
    • Related Report
      2010 Final Research Report
  • [Presentation] 輸血細菌感染症対策細菌迅速遺伝子診断システムを用いた初流血除去の細菌除去効果の判定2008

    • Author(s)
      阿部久美子、田中由美、今井重美、丸山美津子、葛西千枝子、西尾緑、信田憲行、森口洋子、和田英夫、大石晃嗣、小島精、登勉、桝屋正浩
    • Organizer
      第56回輸血・細胞治療学会総会
    • Place of Presentation
      福岡、口演
    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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