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Development of innovative human tumor models using cell patch method for high-speed three-dimensional organization

Research Project

Project/Area Number 19H04454
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 90110:Biomedical engineering-related
Research InstitutionTokyo Women's Medical University

Principal Investigator

Nakayama Masamichi  東京女子医科大学, 医学部, 講師 (00338980)

Co-Investigator(Kenkyū-buntansha) 増田 信奈子  東京女子医科大学, 医学部, 助教 (30342851)
関根 秀一  東京女子医科大学, 医学部, 准教授 (60541737)
原口 裕次  東京女子医科大学, 医学部, 特任准教授 (80272251)
秋元 淳  国立研究開発法人理化学研究所, 創発物性科学研究センター, 研究員 (80649682)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2022: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2021: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywords細胞パッチ / がん細胞 / 過重力 / がん組織工学 / 腫瘍モデル / 担癌モデル動物 / 灌流培養
Outline of Research at the Start

薬物スクリーニングの精度と重要性を高めるためには、実際のがん組織の形態的・機能的特徴を有する組織モデルを効率的に作製する新しい技術が必要である。本研究では、温調制御した遠心操作により、がん細胞およびその関連細胞を高密度充填組織化したがん前駆組織体(がん細胞パッチ)を作製する。がん細胞パッチの構造的・機能的特徴を明らかにしながら、より生体がんに近いin vitro灌流がん組織モデルとin vivo移植がんモデルを構築することで、創薬研究や個別化医療への応用に向けた高い生産性と汎用性、低コスト化を実現する新しいがん組織工学を追究する。

Outline of Final Research Achievements

Well-defined cancer progenitor tissues (cancer cell patches) with a stable sheet-like structure and high-density packing organization of human cancer-derived cells were prepared by optimizing the hypergravity addition and the duration of action. While clarifying the structural and functional characteristics of cancer cell patches, we will construct cancer models that more closely resemble living cancers to pursue new cancer tissue engineering that is highly productive, versatile, and low-cost for application in drug discovery research and personalized medicine. Various cell patches with different sizes, shapes, and thicknesses were able to be effectively obtained by changing the silicone inserts used and the number of applied cells. In addition, the transplantation of the cancer cell patches into immunodeficient animal models resulted in more efficient tumorigenesis compared to the general cell injection method.

Academic Significance and Societal Importance of the Research Achievements

ヒト癌由来細胞から作製したシート状高密度細胞組織であるがん細胞パッチは、形状やサイズの調節や3次元組織化も容易であり、高い汎用性と生産性を有することが明らかとなった。また、生体内移植により高い腫瘍形成能を有しており、新しい生体外がん前駆体としての特徴が示された。今後、がん細胞パッチの構造的・機能的特徴を明らかにしながら、より生体がんに近いがんモデルを構築することで、創薬研究や個別化医療への応用に向けた高い生産性と汎用性、低コスト化を実現する新しいがん組織工学が期待された。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (12 results)

All 2022 2021 2020 2019

All Journal Article (3 results) (of which Peer Reviewed: 2 results) Presentation (9 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results)

  • [Journal Article] Water stable nanocoatings of poly(N-isopropylacrylamide)-based block copolymers on culture insert membranes for temperature-controlled cell adhesion2020

    • Author(s)
      Nakayama Masamichi、Toyoshima Yuki、Chinen Hiroshi、Kikuchi Akihiko、Yamato Masayuki、Okano Teruo
    • Journal Title

      Journal of Materials Chemistry B

      Volume: 8 Issue: 34 Pages: 7812-7821

    • DOI

      10.1039/d0tb01113d

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Micropatterned Smart Culture Surfaces via Multi‐Step Physical Coating of Functional Block Copolymers for Harvesting Cell Sheets with Controlled Sizes and Shapes2020

    • Author(s)
      Nakayama Masamichi、Toyoshima Yuki、Kikuchi Akihiko、Okano Teruo
    • Journal Title

      Macromolecular Bioscience

      Volume: 21 Issue: 3 Pages: 2000330-2000330

    • DOI

      10.1002/mabi.202000330

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] リビングラジカル重合-可逆的付加開裂連鎖移動重合2020

    • Author(s)
      中山正道
    • Journal Title

      Drug Delivery System

      Volume: 36 Pages: 69-71

    • Related Report
      2020 Annual Research Report
  • [Presentation] ポリスチレン表面改質が 温度応答性培養基材の細胞接着性に及ぼす影響とその応用2022

    • Author(s)
      中山正道、岡野光夫
    • Organizer
      第71回高分子討論会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ポリスチレンベース基材の表面改質が温度応答性ナノ薄膜表面への細胞接着に及ぼす影響2022

    • Author(s)
      中山正道、岡野光夫
    • Organizer
      第44回日本バイオマテリアル学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Micropatterned Thermoresponsive Surfaces via Physical Block Copolymer Coatings for Fabricating Cell Sheets with Designed Morphological Structures2022

    • Author(s)
      Nakayama Masamichi, Tonegawa Junichi, Kikuchi Akihiko, Okano Teruo
    • Organizer
      2022 Hawaii-Joint Symposium-SFB+JSB
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Micropatterned Smart Surfaces via Physical Polymer Coatings for Fabricating Cell Sheets with On-demand Morphological Structures2021

    • Author(s)
      Nakayama Masamichi, Tonegawa Junichi, Kikuchi Akihiko, Okano Teruo
    • Organizer
      The 43rd Annual Meeting of the Japanese Society for Biomaterials and the 8th Asian Biomaterials Congress
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Transplantation of sheet-like cancer cell tissues for orthotopic tumor-bearing animal models2020

    • Author(s)
      Nakayama Masamichi、Akimoto Jun、Okano Teruo
    • Organizer
      47th Annual Meeting of the Controlled Release Society
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Stimuli-responsive polymer nanocoatings on culture substrates for smart cell adhesion control2020

    • Author(s)
      Nakayama Masamichi
    • Organizer
      The 30th Frontier Scientists Workshop
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ポリマースタンプ法で作製したパターン化スマート表面を用いた細胞シートの構造制御2020

    • Author(s)
      中山正道、利根川純一、菊池明彦、大和雅之、岡野光夫
    • Organizer
      第15回ナノ・バイオメディカル学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 親水性基を導入した温度応答性ブロック共重合体コート表面における細胞接着/脱着挙動2020

    • Author(s)
      北嶋健太郎、中山正道、菊池明彦、岡野光夫
    • Organizer
      第69回高分子討論会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Controlled structure of cell sheets using micropatterned thermoresponsive surfaces prepared by polymer stamping method2019

    • Author(s)
      Masamichi Nakayama, Junichi Tonegawa, Akihiko Kikuchi, Teruo Okano
    • Organizer
      30th Annual Conference of the European Society for Biomaterials
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2024-01-30  

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