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マイクロ工学によるがん微小環境モデルの構築

Research Project

Project/Area Number 15F15767
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section外国
Research Field Nano/Microsystems
Research InstitutionThe University of Tokyo

Principal Investigator

松永 行子 (津田行子)  東京大学, 生産技術研究所, 講師 (00533663)

Co-Investigator(Kenkyū-buntansha) PAUTY JORIS  東京大学, 生産技術研究所, 外国人特別研究員
Project Period (FY) 2015-11-09 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2017: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2016: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2015: ¥800,000 (Direct Cost: ¥800,000)
Keywordsin vitro model / tissue engineering / vascular biology / cancer / blood cessel / barrier function / angiogenesis / tumor microenvironment / organ on a chip
Outline of Annual Research Achievements

本研究ではマイクロ加工技術を用いた三次元の微小血管構造の作製により、血管新生と血管透過性の双方を計測しうる新規な評価系の構築を目的とした。ヒト血管内皮細胞を用いた管腔状の三次元微小血管モデルを構築し、血管新生挙動の再現と血管透過性制御についての有用性について検証を行った。微小血管モデルに血管内皮増殖因子を一定期間添加すると血管内皮細胞がデバイス中のコラーゲンゲル領域へ出芽し新生血管が形成され、抗血管新生薬(VEGFR阻害薬:ソラフェニブおよびスニチニブ)で処理すると血管新生は抑制されることを確認した。蛍光デキストラン分子(70 kDa)を血管内へ導入することにより血管透過性を評価したところ、スニチニブで処理した血管はバリア機能を有するのに対し、ソラフェニブで処理をした血管ではバリア機能が亢進していることを確認した。以上より、開発した微小血管モデルは、血管新生誘導因子および抑制因子に応答能を示し、血管新生および血管透過性の双方を観察可能なモデルとして有用であることが実証された。本研究で検討したスニチニブおよびソラフェニブのように多くの抗血管新生薬は、様々な経路を阻害するマルチキナーゼ阻害薬であり、VEGFの効果を阻害し血管新生を食い止めるだけでなく、副次的に他の作用反応も誘発される。よって今回開発した評価手法は、薬効評以外に、4件の論文(原著論文3件・研究解説1件)としてまとめられ、プレスリリースを行い、日経新聞、World Pharma Newsなどで紹介された。

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (33 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (3 results) Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 3 results,  Open Access: 4 results) Presentation (18 results) (of which Int'l Joint Research: 8 results,  Invited: 8 results) Book (1 results) Remarks (7 results)

  • [Int'l Joint Research] CNRS/INSERM/Lille Pasteur Institute(France)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] パスツール研究所・リール生物学研究所/Ecole Normale Superieure/リール第一大学(フランス)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] CNRS/INSERM(France)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] A Vascular Endothelial Growth Factor-Dependent Sprouting Angiogenesis Assay Based on an In Vitro Human Blood Vessel Model for the Study of Anti-Angiogenic Drugs2018

    • Author(s)
      Pauty Joris、Usuba Ryo、Cheng Irene Gayi、Hespel Louise、Takahashi Haruko、Kato Keisuke、Kobayashi Masayoshi、Nakajima Hiroyuki、Lee Eujin、Yger Florian、Soncin Fabrice、Matsunaga Yukiko T.
    • Journal Title

      EBioMedicine

      Volume: 27 Pages: 225-236

    • DOI

      10.1016/j.ebiom.2017.12.014

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A 3D in vitro pericyte-supported microvessel model: visualisation and quantitative characterisation of multistep angiogenesis2018

    • Author(s)
      Lee Eujin、Takahashi Haruko、Pauty Joris、Kobayashi Masayoshi、Kato Keisuke、Kabara Maki、Kawabe Jun-ichi、Matsunaga Yukiko T.
    • Journal Title

      Journal of Materials Chemistry B

      Volume: 6 Issue: 7 Pages: 1085-1094

    • DOI

      10.1039/c7tb03239k

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A vascular permeability assay using an in vitro human microvessel model mimicking the inflammatory condition2017

    • Author(s)
      Joris Pauty, Ryo Usuba, Haruko Takahashi, Junichi Suehiro, Kanoko Fujisawa, Kiichiro Yano, Tomohiro Nishizawa, Yukiko T. Matsunaga
    • Journal Title

      Nanotheranostics

      Volume: 1 Issue: 1 Pages: 103-113

    • DOI

      10.7150/ntno.18303

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An <i>In Vitro</i> Microvessel Model Mimicking the Inflammatory Condition for Evaluation of Barrier Function2017

    • Author(s)
      薄葉 亮、ジョリス ポティ、高橋 治子、末弘 淳一、松永 行子
    • Journal Title

      SEISAN KENKYU

      Volume: 69 Issue: 3 Pages: 127-132

    • DOI

      10.11188/seisankenkyu.69.127

    • NAID

      130005682804

    • ISSN
      0037-105X, 1881-2058
    • Related Report
      2017 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Presentation] 人工微小血管モデルによる薬剤応答性の血管透過性評価2017

    • Author(s)
      薄葉亮、Joris Pauty、高橋治子、末弘淳一、松永行子
    • Organizer
      第26回インテリジェント材料・システムシンポジウム
    • Place of Presentation
      東京女子医科大学先端生命医科学研究所、新宿
    • Year and Date
      2017-01-11
    • Related Report
      2016 Annual Research Report
  • [Presentation] 三次元微小血管チップによる血管新生および血管透過性評価法の提案2017

    • Author(s)
      松永行子
    • Organizer
      心血管代謝週間(CVMW2017)
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 血管組織をデザインし組み立てる新技術2017

    • Author(s)
      松永行子
    • Organizer
      2017年度生命科学系学会合同年次大会(conbio2017)
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 「細胞で創る」微小血管システム - Microvessel system fabricated from cells-2017

    • Author(s)
      松永行子
    • Organizer
      「細胞を創る」研究会10.0
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 生体組織工学による血管微小環境の見える化2017

    • Author(s)
      松永行子
    • Organizer
      Tie2・リンパ・血管研究会第3回学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Bottom-up tissue engineering for building tissue microenvironment2017

    • Author(s)
      Y.T. Matsunaga
    • Organizer
      FEBS workshop -Biological Surfaces and Interfaces: Interface Dynamics-
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 組織構築による生体現象のみえる化2017

    • Author(s)
      松永行子
    • Organizer
      第17回東京大学生命科学シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Engineering In Vitro Microvasculature For Drug-Responsive Permeability Assay2016

    • Author(s)
      Ryo Usuba, Joris Pauty, Haruko Takahashi, Kanoko Fujisawa, Junichi Suehiro, Kiichiro Yano, Tomohiro Nishizawa, Yukiko T. Matsunaga
    • Organizer
      TERMIS-AM meeting - December 11th-14th 2016
    • Place of Presentation
      Manchester Grand Hyatt, San Diego (CA), USA
    • Year and Date
      2016-12-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Characterization of cellulosic-based bundled gel fibers as a potential scaffold for neuron regeneration2016

    • Author(s)
      G. Garcia, H. Takahashi , S. Tachizawa, J. Pauty, Y.T. Matsunaga
    • Organizer
      TERMIS-AM meeting - December 11th-14th 2016
    • Place of Presentation
      Manchester Grand Hyatt, San Diego (CA), USA
    • Year and Date
      2016-12-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In vitro microvasculature model using genetically engineered cells2016

    • Author(s)
      J. Pauty, H. Takahashi, F. Soncin, Y.T. Matsunaga
    • Organizer
      TERMIS-AM meeting - December 11th-14th 2016
    • Place of Presentation
      Manchester Grand Hyatt, San Diego (CA), USA
    • Year and Date
      2016-12-11
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 微小血管透過性評価モデル構築のための細胞間結合評価2016

    • Author(s)
      薄葉亮、Joris Pauty、高橋治子、藤澤佳乃子、末弘淳一、矢野喜一郎、西澤友宏、松永行子
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜、横浜
    • Year and Date
      2016-12-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] Microengineered Collagen-based Vasculature Model for Evaluating Endothelial Permeability2016

    • Author(s)
      Ryo Usuba, Joris Pauty, Haruko Takahashi, Kanoko Fujisawa, Junichi Suehiro, Kiichiro Yano, Tomohiro Nishizawa, Yukiko T. Matsunaga
    • Organizer
      3rd International Conference on Biomaterials Science in Tokyo
    • Place of Presentation
      東京大学伊藤国際学術研究センター、東京
    • Year and Date
      2016-11-28
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In vitro microvasculature model simulating a diseased blood vessel2016

    • Author(s)
      J. Pauty, H. Takahashi, F. Soncin, Y.T. Matsunaga
    • Organizer
      ICBS2016, 3rd International Conference on Biomaterials Science in Tokyo - November 28th-30th 2016
    • Place of Presentation
      the University of Tokyo, Hongo campus, Tokyo, Japan
    • Year and Date
      2016-11-18
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Microfluidic-Fabrication Of Cellulosic-Based bundled gel fibres as cell culture scaffold2016

    • Author(s)
      Y.T. Matsunaga, S. Jakaratanopas, G. Garcia, S. Tachizawa, H. Takahashi, J. Pauty
    • Organizer
      Biomaterials International 2016
    • Place of Presentation
      Kenting, Taiwan
    • Year and Date
      2016-11-01
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In vitro 3D microvasculature models to simulate diseased and healthy state2016

    • Author(s)
      J. Pauty, H. Takahashi, F. Soncin, Y.T. Matsunaga
    • Organizer
      Gordon Research Conference, Endothelial Cell Phenotypes in Health & Disease - July 17th-22nd 2016
    • Place of Presentation
      PGA Catalunya Business and Convention Centre, Girona, Spain
    • Year and Date
      2016-07-20
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ボトムアップ組織工学による生体組織構造の構築2016

    • Author(s)
      松永行子
    • Organizer
      医用・生体工学研究会
    • Place of Presentation
      東京大学先端科学技術研究センター, 東京
    • Year and Date
      2016-03-22
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] マイクロ加工技術を利用した生体組織構造のデザイン:血管新生モデル2016

    • Author(s)
      松永行子
    • Organizer
      第4回次世代がん治療推進専門家養成プランシンポジウム
    • Place of Presentation
      東京医科歯科大学, 東京
    • Year and Date
      2016-01-23
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Microvasculature Chip for Angiogenesis Study2015

    • Author(s)
      Y.T. Matsunaga, F. Soncin
    • Organizer
      Workshop on BioMEMS and Cancer
    • Place of Presentation
      IBL, Lille, France
    • Year and Date
      2015-12-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Book] 臓器チップの技術と開発動向 監修:酒井康行・金森敏幸2018

    • Author(s)
      薄葉亮,松永行子
    • Total Pages
      293
    • Publisher
      シーエムシー出版
    • ISBN
      9784781313252
    • Related Report
      2017 Annual Research Report
  • [Remarks] 研究室ホームページ

    • URL

      http://www.matlab.iis.u-tokyo.ac.jp/index.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] プレスリリース

    • URL

      https://www.iis.u-tokyo.ac.jp/ja/research/archive/2853/

    • Related Report
      2017 Annual Research Report
  • [Remarks] Science Daily

    • URL

      https://www.sciencedaily.com/releases/2018/01/180130090832.htm

    • Related Report
      2017 Annual Research Report
  • [Remarks] World Pharma News

    • URL

      http://www.worldpharmanews.com/research/4277-blood-vessel-on-a-chips-show-anti-cancer-drug-effects-in-human-cells

    • Related Report
      2017 Annual Research Report
  • [Remarks] 東京大学生産技術研究所松永研究室

    • URL

      http://www.matlab.iis.u-tokyo.ac.jp/index.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] LIMMS/CNRS-IIS (2820) 国際連携研究センター

    • URL

      https://www.iis.u-tokyo.ac.jp/ja/research/department_center/limms/

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
  • [Remarks] Matsunaga laboratory, IIS, UTokyo

    • URL

      http://www.matlab.iis.u-tokyo.ac.jp/index.html

    • Related Report
      2015 Annual Research Report

URL: 

Published: 2015-11-26   Modified: 2024-03-26  

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