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2012 Fiscal Year Research-status Report

薬物刺激間葉系幹細胞を用いたDual Stem Cell Therapyの開発

Research Project

Project/Area Number 24659461
Research InstitutionKyoto University

Principal Investigator

前川 平  京都大学, 医学(系)研究科(研究院), 教授 (80229286)

Co-Investigator(Kenkyū-buntansha) 三浦 康生  京都大学, 医学(系)研究科(研究院), 助教 (70605146)
平位 秀世  京都大学, 医学(系)研究科(研究院), 助教 (50315933)
Project Period (FY) 2012-04-01 – 2014-03-31
Keywords間葉系幹細胞
Research Abstract

難治性血液がんに対する臍帯血移植では移植前処置により破壊された造血組織は造血幹細胞によりレスキューされる。本研究課題では移植前処置により障害を受けた非造血組織を間葉系幹細胞を応用してレスキューするための基礎的データの蓄積を目指す。間葉系幹細胞は組織修復・造血支持力を有する組織幹細胞である。さい帯血にも含まれるが、その存在頻度は低く有核細胞数10の6乗個から10の7乗個に1個程度と考えられている。我々は、従来の方法より効率的にさい帯血から間葉系幹細胞を分離・培養する方法を確立した。接着法を用いた標準的な間葉系幹細胞分離方法では浮遊細胞は培養早期に除去される。さい帯血細胞からの間葉系幹細胞の分離・培養過程において、浮遊細胞を早期に除去せず培養を継続することで、間葉系幹細胞の分離・培養効率が約10倍に改良された。得られた細胞は従来の方法で得られた間葉系幹細胞と同様の性質を有していた。以上の結果は存在頻度の少ない間葉系幹細胞を効率的分離・培養増幅することで治療特性が増強され、臍帯血移植において高い組織修復力が得られる可能性があると考えられた。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

さい帯血からの間葉系幹細胞の分離・培養過程において、浮遊細胞を早期に除去せず培養を継続することで、間葉系幹細胞の分離・培養効率が約10倍に改良された。さい帯血からの間葉系幹細胞の分離・培養は一般に容易でないことが知られているが、本研究課題によりその改良が得られたためである。

Strategy for Future Research Activity

間葉系幹細胞を効率的に分離・培養増幅することで量的な治療効果を得ることを目指す。また、従来の方法で得られる間葉系幹細胞との違いを検討することで治療特性を明らかにする。さらに、培養増幅した間葉系幹細胞を薬物刺激することで質的な治療効果の向上を目指す。これらにより造血幹細胞と間葉系幹細胞を共移植するDual Stem Cell Therapyの技術開発を目指す。

Expenditure Plans for the Next FY Research Funding

研究に必要な設備備品は既に整備されており、研究費による購入の予定はない。研究費は細胞培養関連試薬(液体培地、ウシ血清、サイトカインなど)の購入、試薬・抗体の購入、実験動物(免疫不全マウスなど)の購入・維持に充てる計画である。また、研究成果発表のための学会参加や論文発表、新規情報収集のための学会参加にも研究費を使用する予定である。

  • Research Products

    (27 results)

All 2013 2012

All Journal Article (13 results) (of which Peer Reviewed: 11 results) Presentation (14 results)

  • [Journal Article] Combination of ponatinib with Hedgehog antagonist vismodegib for therapy-resistant BCR-ABL1 positive leukemia.2013

    • Author(s)
      Katagiri S
    • Journal Title

      Clin Cancer Res

      Volume: 19(6) Pages: 1422-1432

    • DOI

      10.1158/1078-0432.CCR-12-1777

    • Peer Reviewed
  • [Journal Article] Effectiveness of sulforaphane as a radiosensitizer for murine osteosarcoma cells.2013

    • Author(s)
      Sawai Y
    • Journal Title

      Oncol Rep

      Volume: 29 (3) Pages: 941-945

    • DOI

      10.3892/or.2012.2195

    • Peer Reviewed
  • [Journal Article] Zoledronic acid significantly enhances radiation induced apoptosis against human fibrosarcoma cells by inhibiting radioadaptive signaling.2013

    • Author(s)
      Koto K
    • Journal Title

      Int J Oncol

      Volume: 42 (2) Pages: 525-534

    • DOI

      10.3892/ijo.2012.1735

    • Peer Reviewed
  • [Journal Article] Activity of histone deacetylase inhibitors and an Aurora kinase inhibitor in BCR-ABL expressing leukemic cells.2013

    • Author(s)
      Okabe S
    • Journal Title

      Cancer Cell International

      Volume: 13 (1) Pages: 32-40

    • DOI

      10.1186/1475-2867-13-32

    • Peer Reviewed
  • [Journal Article] C/EBPβ promotes BCR-ABL-mediated myeloid expansion and leukemic stem cell exhaustion.2013

    • Author(s)
      Hayashi Y
    • Journal Title

      Leukemia

      Volume: 27 (3) Pages: 619-628

    • DOI

      10.1038/leu.2012.258

    • Peer Reviewed
  • [Journal Article] Cyclic AMP Responsive Element Binding Proteins Are Involved in ‘Emergency’ Granulopoiesis through the Upregulation of CCAAT/Enhancer Binding Protein β.2013

    • Author(s)
      Hirai H
    • Journal Title

      PLoS ONE

      Volume: 8 (1) Pages: 該当なし

    • DOI

      10.1371/journal.pone.0054862

    • Peer Reviewed
  • [Journal Article] An exploratory clinical study on the safety and efficacy of an autologous fibroblast-seeded artificial skin cultured with animal product-free medium in patients with diabetic foot ulcers.2012

    • Author(s)
      Morimoto N
    • Journal Title

      Int Wound J

      Volume: 9 Pages: 1-8

    • DOI

      10.1111/j.1742-481X.2012.01064.x

    • Peer Reviewed
  • [Journal Article] C/EBPβ is involved in the amplification of early granulocyte precursors during candidemia-induced ‘emergency’ granulopoiesis.2012

    • Author(s)
      Satake S
    • Journal Title

      J Immunol

      Volume: 189 (9) Pages: 4546-4555

    • DOI

      10.4049/jimmunol.1103007

    • Peer Reviewed
  • [Journal Article] Progressive graft fibrosis and donor-specific HLA antibodies in pediatric late liver allografts.2012

    • Author(s)
      Miyagawa-Hayashino A
    • Journal Title

      Liver Transpl

      Volume: 18 (11) Pages: 1333-1342

    • DOI

      10.1002/lt. 23534

    • Peer Reviewed
  • [Journal Article] Effects of low-intensity pulsed ultrasound (LIPUS) on osteosarcoma and cancer cells.2012

    • Author(s)
      Sawai Y
    • Journal Title

      Oncol Rep

      Volume: 28 (2) Pages: 481-486

    • DOI

      10.3892/or.2012.1816

    • Peer Reviewed
  • [Journal Article] Incidence and pattern of hemolytic anemia after minor ABO-mismatched living-donor lobar lung transplantation.2012

    • Author(s)
      Ohsumi A
    • Journal Title

      Surg Today

      Volume: 70 (2) Pages: 211-245

    • Peer Reviewed
  • [Journal Article] 造血器腫瘍の診断と治療 治療法 支持療法;輸血副作用とHLA抗体.2012

    • Author(s)
      吉岡聡
    • Journal Title

      日本臨床

      Volume: 70 (2) Pages: 211-245

  • [Journal Article] 細胞周期調節系.2012

    • Author(s)
      前川 平
    • Journal Title

      日本臨牀

      Volume: 70 (suppl 8) Pages: 119-124

  • [Presentation] C/EBPβ is upregulated through STAT5 and accelerates exhaustion of leukemic stem cells in chronic phase of chronic myeloid leukemia.2012

    • Author(s)
      Hayashi Y
    • Organizer
      The 54th ASH Annual Meeting and Exposition
    • Place of Presentation
      Atlanta, GA, USA
    • Year and Date
      20121211-20121211
  • [Presentation] Expression of C/EBPβ in Bone Marrow Mesenchymal Stem Cells Is Mandatory for Early-Stage B Cell Lymphopoiesis.2012

    • Author(s)
      Yoshioka S
    • Organizer
      The 54th ASH Annual Meeting and Exposition
    • Place of Presentation
      Atlanta, GA, USA
    • Year and Date
      20121210-20121210
  • [Presentation] Mesenchymal stem cells skewed their phenotype toward the osteogenic lineage support the hematopoietic cell differentiation.2012

    • Author(s)
      Yao H
    • Organizer
      The 54th ASH Annual Meeting and Exposition
    • Place of Presentation
      Atlanta, GA, USA
    • Year and Date
      20121210-20121210
  • [Presentation] C/EBPβ-mediated expansion of hematopoietic stem/progenitors precedes ‘emergency’ granulopoiesis induced by candidemia.2012

    • Author(s)
      Tamura A
    • Organizer
      The 54th ASH Annual Meeting and Exposition
    • Place of Presentation
      Atlanta, GA, USA
    • Year and Date
      20121209-20121209
  • [Presentation] Myeloid-derived suppressor cells accumulated in spleens of mice with collagen-induced arthritis and inhibited immune response of CD4+ T cells.2012

    • Author(s)
      Fujii W
    • Organizer
      American College of Rheumatology 2012 Annual Scientific Meeting
    • Place of Presentation
      Washington, DC, USA
    • Year and Date
      20121113-20121113
  • [Presentation] Parathyroid hormone stimulates mesenchymal stem cells to enhance expansion of hematopoietic cells.2012

    • Author(s)
      Yao H
    • Organizer
      The 74th Annual Meeting of the Japanese Society of Hematology
    • Place of Presentation
      国際会議場(京都府)
    • Year and Date
      20121020-20121020
  • [Presentation] Defective mesenchymal stem cells contribute to impaired B cell lymphopoiesis in C/EBPb knockout mice.2012

    • Author(s)
      Yoshioka S
    • Organizer
      The 74th Annual Meeting of the Japanese Society of Hematology
    • Place of Presentation
      国際会議場(京都府)
    • Year and Date
      20121020-20121020
  • [Presentation] Co-treatment with ponatinib and HDAC inhibitor vorinostat: A treatment for Ph-positive cells.2012

    • Author(s)
      Okabe S
    • Organizer
      The 74th Annual Meeting of the Japanese Society of Hematology
    • Place of Presentation
      国際会議場(京都府)
    • Year and Date
      20121020-20121020
  • [Presentation] Targeting the Hedgehog pathway in therapy-resistant BCR-ABL1 positive leukemia with ponatinib.2012

    • Author(s)
      Katagiri S
    • Organizer
      The 74th Annual Meeting of the Japanese Society of Hematology
    • Place of Presentation
      国際会議場(京都府)
    • Year and Date
      20121020-20121020
  • [Presentation] Combined effects of ponatinib and dasatinib against T315I mutant forms of BCR-ABL1.2012

    • Author(s)
      Tauchi T
    • Organizer
      The 74th Annual Meeting of the Japanese Society of Hematology
    • Place of Presentation
      国際会議場(京都府)
    • Year and Date
      20121020-20121020
  • [Presentation] 新規Wnt/beta-カテニン経路阻害剤AV65による多発性骨髄腫細胞の増殖抑制効果.2012

    • Author(s)
      芦原英司
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      ロイトン札幌(北海道)
    • Year and Date
      20120920-20120920
  • [Presentation] An exploratory clinical study on the safety and efficacy of an autologous fibroblast-seeded artificial skin cultured with animal-product free medium in patients with diabetic foot ulcers.2012

    • Author(s)
      Morimoto N
    • Organizer
      4th Congress of the World Union of Wound Healing Societies
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      20120902-20120906
  • [Presentation] BCR/ABLの白血病原性における転写因子 C/EBPβの関与.2012

    • Author(s)
      林 嘉宏
    • Organizer
      第16回日本がん分子標的治療学会学術集会
    • Place of Presentation
      西日本総合展示場(福岡県)
    • Year and Date
      20120628-20120628
  • [Presentation] Successful co-treatment of BCR-ABL leukemic cells with ponatinib, an ABL kinase inhibitor, and vorinostat, a histone deacetylase inhibitor: A potential treatment for BCR-ABL positive leukemia cells.2012

    • Author(s)
      Okabe S
    • Organizer
      17th Congress of European Society of Hematology
    • Place of Presentation
      Amsterdam, The Netherland
    • Year and Date
      20120614-20120617

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Published: 2014-07-24  

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