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Genetically-engineered multilineage-differentiating stress-enduring cells as cellular vehicles against malignant gliomas

Research Project

Project/Area Number 25293306
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Namba Hiroki  浜松医科大学, 医学部, 教授 (60198405)

Co-Investigator(Kenkyū-buntansha) 天野 慎士  浜松医科大学, 医学部, 特任研究員 (70464138)
徳山 勤  浜松医科大学, 医学部附属病院, 講師 (90313957)
Co-Investigator(Renkei-kenkyūsha) DEZAWA MARI  東北大学, 医学部, 教授 (50272323)
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Keywordsglioma / gene therapy / stem cells / bystander effect / migration / viral thymidine kinase / ganciclovir / 遺伝子治療 / 悪性グリオーマ / 多能性幹細胞 / ガンシクロビル / チミジンキナーゼ / 遊走能
Outline of Final Research Achievements

Suicide gene therapy based on the herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) is an efficient strategy for treating malignant gliomas. In the present study, we evaluated treatment with multilineage-differentiating stress-enduring (Muse) cells, endogenous non- tumorigenic pluripotent-like stem cells, as carriers of the HSVtk gene. HSVtk gene-transduced human Muse cells (Muse-tk cells) showed a potent in vivo bystander effect and migratory activity toward glioma cells. Intracranial U87 gliomas in nude mouse brains injected intratumorally with Muse-tk cells followed by intraperitoneal GCV administration were significantly reduced in size within 2 weeks. These findings suggest that intratumoral Muse-tk cell injection followed by systemic GCV administration is safe and effective, and that allogeneic Muse-tk cell-medicated suicide gene therapy for malignant glioma is clinically feasible.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (22 results)

All 2017 2016 2015 2014 2013

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (17 results) (of which Invited: 3 results)

  • [Journal Article] Shear Stiffness of 4 Common Intracranial Tumors Measured Using MR Elastography: Comparison with Intraoperative Consistency Grading2017

    • Author(s)
      Sakai N, Takehara Y, Yamashita S, Oishi N, Kawaji H, Sameshima T, Baba S, Sakahara H, Namba H
    • Journal Title

      AJNR Am J Neuroradiol

      Volume: 36 Issue: 10 Pages: 1851-1859

    • DOI

      10.3174/ajnr.a4832

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The efficacy of resection of an intradural extramedullary foramen magnum cavernous malformation presenting with repeated subarachnoid hemorrhage2017

    • Author(s)
      Oishi T, Sakai N, Sameshima T, Kawaji H, Namba H
    • Journal Title

      J Med Case Reports

      Volume: 11 Issue: 1 Pages: 63-63

    • DOI

      10.1186/s13256-017-1220-8

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Use of genetically engineered stem cells for glioma therapy2016

    • Author(s)
      Namba H, Kawaji H, Yamasaki T
    • Journal Title

      Oncol Lett

      Volume: 11 Pages: 9-15

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interferon-β and temozolomide combination therapy for temozolomide monotherapy-refractory malignant gliomas2015

    • Author(s)
      Kawaji H, Tokuyama T, Yamasaki T, Amano S, Sakai N, Namba H
    • Journal Title

      Mol Clin Oncol

      Volume: 3 Pages: 909-913

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Potent tumor tropism of induced pluripotent stem cells and induced pluripotent stem cell-derived neural stem cells in the mouse intracerebral glioma model2015

    • Author(s)
      Yamazoe T, Koizumi S, Yamasaki T, Amano S, Tokuyama T, Namba H
    • Journal Title

      Int J Oncol

      Volume: 46 Issue: 1 Pages: 147-152

    • DOI

      10.3892/ijo.2014.2702

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 遺伝子導入ミューズ細胞を刺客として用いるグリオーマの遺伝子細胞治療2016

    • Author(s)
      難波宏樹、山﨑友裕、小泉慎一郎、釼持博昭、若尾昌平、出澤真理
    • Organizer
      第34回日本脳腫瘍学会
    • Place of Presentation
      甲府
    • Year and Date
      2016-12-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] 悪性グリオーマに対する刺客細胞としての遺伝子導入Muse細胞の応用2016

    • Author(s)
      崎友裕、釼持博昭、難波宏樹
    • Organizer
      第75回日本癌学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] HSV遺伝子導入Muse細胞の腫瘍指向性を用いた新規悪性グリオーマ治療戦略2016

    • Author(s)
      山崎友裕、難波宏樹
    • Organizer
      第75回日本脳神経外科学会総会
    • Place of Presentation
      博多
    • Year and Date
      2016-09-29
    • Related Report
      2016 Annual Research Report
  • [Presentation] Geneticlly-engineered multilineage-differentiated stess-enduring (MUSE) cells as a cellular assassins against malignant gliomas2016

    • Author(s)
      Namba H, Yamasaki T, Wakao S, Dezawa M
    • Organizer
      第22回日本遺伝子細胞治療学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2016-07-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] HSVtk遺伝子導入Muse細胞を用いたグリオーマの自殺遺伝子幹細胞治療2015

    • Author(s)
      山崎友裕
    • Organizer
      第74回日本脳神経外科学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2015-10-14
    • Related Report
      2015 Annual Research Report
  • [Presentation] HSVtk遺伝子導入Muse細胞を用いたグリオーマの遺伝子治療2015

    • Author(s)
      山崎友裕
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] 脳腫瘍治療の最新知見と核医学の役割2015

    • Author(s)
      難波宏樹
    • Organizer
      第61回関東核医学画像処理研究会
    • Place of Presentation
      東京
    • Year and Date
      2015-09-26
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] グリオーマの最新治療2015

    • Author(s)
      難波宏樹
    • Organizer
      横浜サイバーナイフセンター設立10周年記念講演会
    • Place of Presentation
      横浜
    • Year and Date
      2015-09-04
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Integration-free methodにて作成したHSVtk遺伝子導入iPS細胞由来神経幹細胞はグリオーマに対するリン酸化ガンシクロビルの適した媒体となる2015

    • Author(s)
      山崎友裕
    • Organizer
      第16回日本分子脳神経外科学会
    • Place of Presentation
      浜松
    • Year and Date
      2015-08-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] Stem Cell-based Gene Therapy for Malignant Brain Tumors2015

    • Author(s)
      Hiroki Namba
    • Organizer
      International Symposium toward the Future of Advanced Researches in Shizuoka University
    • Place of Presentation
      Hamamatsu
    • Year and Date
      2015-01-27 – 2015-01-28
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] HSVtk遺伝子導入Muse細胞を用いたグリオーマの遺伝子細胞療法2014

    • Author(s)
      難波宏樹
    • Organizer
      第32回日本脳腫瘍学会
    • Place of Presentation
      舞浜
    • Year and Date
      2014-11-30 – 2014-12-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] Suicide gene therapy for glioma using multilineage-differentiating stress enduring (Muse) cells2014

    • Author(s)
      山﨑友裕
    • Organizer
      第15回日本分子脳神経外科学会
    • Place of Presentation
      山形
    • Year and Date
      2014-09-25 – 2014-09-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Potent in vivo bystander effect of the suicide gene therapy to glioblastoma using Muse cells transduced with herpes simplex virus thymidine kinase gene and ganciclovir2014

    • Author(s)
      難波宏樹
    • Organizer
      第20回日本遺伝子治療学会
    • Place of Presentation
      東京
    • Year and Date
      2014-08-06 – 2014-08-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] Suicide gene therapy for glioma using induced pluripotent stem cell-derived neural stem cells generated without using viral vector2014

    • Author(s)
      山﨑友裕
    • Organizer
      第20回日本遺伝子治療学会
    • Place of Presentation
      東京
    • Year and Date
      2014-08-06 – 2014-08-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] Potent in vitro bystander effect and migratory activity in the suicide gene therapy using Muse cells transduced with herpes simplex virus thymidine kinase gene and ganciclovir2013

    • Author(s)
      難波宏樹
    • Organizer
      第19回日本遺伝子治療学会
    • Place of Presentation
      岡山
    • Related Report
      2013 Annual Research Report
  • [Presentation] Use of Muse cells transduced with herpes simplex virus-thymidine kinase gene for glioma gene therapy2013

    • Author(s)
      山添知宏
    • Organizer
      第72日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Muse細胞をベクターとするグリオーマのHSVtk遺伝子細胞療法2013

    • Author(s)
      難波宏樹
    • Organizer
      第31回日本脳腫瘍学会
    • Place of Presentation
      宮崎
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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