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Reconstruction of tumor microenvironment and in-situ metabolic analysis

Research Project

Project/Area Number 21H03803
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 Medical and Dental University

Principal Investigator

Nashimoto Yuji  東京医科歯科大学, 生体材料工学研究所, 准教授 (80757617)

Co-Investigator(Kenkyū-buntansha) 珠玖 仁  東北大学, 工学研究科, 教授 (10361164)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2023: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2022: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2021: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
KeywordsOrgan-on-a-chip / 生体模倣システム / 走査型プローブ顕微鏡 / 血管 / 走査型電気化学顕微鏡 / マイクロ流体デバイス / がん微小環境 / 電気化学計測 / がん
Outline of Research at the Start

がん細胞は,通常と異なる代謝によってエネルギーを産生しており,がんの代謝機序を明らかにできれば,がん特異的な薬剤開発へ貢献できる.しかし,代謝活動の定量解析には,組織からの細胞の単離が必要であり,この単離操作による代謝活動の変質が課題であった.そこで本研究では,生体内類似のがん微小環境の再現,および「その場」代謝マッピングにより,この課題を解決する.がん微小環境は,マイクロ流体デバイスを用いて再現を行い,特に,既存の手法で困難であった血管周囲の力学環境の制御を実現する.

Outline of Final Research Achievements

In this study, we aimed to establish an in situ metabolic measurement system within the tumor microenvironment and explored the development of a novel platform using scanning electrochemical microscopy (SECM) and microfluidic devices. As a result, by employing microfluidic devices, we successfully constructed a vascular network, which is a critical component of the tumor microenvironment, around patient-derived tumor organoids. This allowed us to stimulate the tumor organoids via the vascular network and capture their metabolic changes using an electrochemical sensor. Furthermore, we demonstrated the potential to evaluate the phenotypic changes of the vascular network surrounding the tumor within the microfluidic device.

Academic Significance and Societal Importance of the Research Achievements

がんの代謝は、古くから注目されている分野であるが、その機序は十分に解明されていない。一因に、複雑性を切り分けることが可能な優れたin vitroモデルが欠如していることが挙げられる。本研究課題では、生体外で生体内のがんの複雑性の一端を担うがん微小環境の構成要素を再構築し、がん代謝への影響を評価するプラットフォームを提案することができた。スループットをはじめ、課題が見られるものの、がん微小環境を紐解く有効な分析手法として期待ができる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (46 results)

All 2024 2023 2022

All Journal Article (15 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 15 results,  Open Access: 10 results) Presentation (31 results) (of which Int'l Joint Research: 5 results,  Invited: 8 results)

  • [Journal Article] Modeling embryo-endometrial interface recapitulating human embryo implantation2024

    • Author(s)
      Shibata Shun、Endo Shun、Nagai Luis A. E.、H. Kobayashi Eri、Oike Akira、Kobayashi Norio、Kitamura Akane、Hori Takeshi、Nashimoto Yuji、Nakato Ryuichiro、Hamada Hirotaka、Kaji Hirokazu、Kikutake Chie、Suyama Mikita、Saito Masatoshi、Yaegashi Nobuo、Okae Hiroaki、Arima Takahiro
    • Journal Title

      Science Advances

      Volume: 10 Issue: 8

    • DOI

      10.1126/sciadv.adi4819

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Three-dimensional-printed Refillable Drug Delivery Device for Long-term Sustained Drug Delivery to Retina2023

    • Author(s)
      Takeshi Hori, Yuya Ito, Bibek Raut, Serge Ostrovidov, Yuji Nashimoto, Nobuhiro Nagai, Toshiaki Abe, Hirokazu Kaji
    • Journal Title

      Sensors and Materials

      Volume: 35 Issue: 4 Pages: 1301

    • DOI

      10.18494/SAM4167

    • ISSN
      0914-4935, 2435-0869
    • Year and Date
      2023-04-11
    • Related Report
      2023 Annual Research Report 2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Engineering Oral Microenvironments Using Microphysiological Systems2023

    • Author(s)
      Yuji Nashimoto, Takeshi Hori, Serge Ostrovidov, Sayaka Katagiri, Hirokazu Kaji
    • Journal Title

      Sensors and Materials

      Volume: 35 Issue: 4 Pages: 1293

    • DOI

      10.18494/SAM4164

    • ISSN
      0914-4935, 2435-0869
    • Year and Date
      2023-04-11
    • Related Report
      2023 Annual Research Report 2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Microfluidic vascular formation model for assessing angiogenic capacities of single islets2023

    • Author(s)
      Nashimoto Yuji、Konno An、Imaizumi Takuto、Nishikawa Kaori、Ino Kosuke、Hori Takeshi、Kaji Hirokazu、Shintaku Hirofumi、Goto Masafumi、Shiku Hitoshi
    • Journal Title

      Biotechnology and Bioengineering

      Volume: 121 Issue: 3 Pages: 1050-1059

    • DOI

      10.1002/bit.28631

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vasculature-on-a-Chip with a Porous Membrane Electrode for In Situ Electrochemical Detection of Nitric Oxide Released from Endothelial Cells2023

    • Author(s)
      Utagawa Yoshinobu、Ino Kosuke、Hiramoto Kaoru、Iwase Kazuyuki、Nashimoto Yuji、Honma Itaru、Shiku Hitoshi
    • Journal Title

      Analytical Chemistry

      Volume: 95 Issue: 49 Pages: 18158-18165

    • DOI

      10.1021/acs.analchem.3c03684

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecularly Imprinted Polymer-Based Sensors for the Detection of Skeletal- and Cardiac-Muscle-Related Analytes2023

    • Author(s)
      Ostrovidov Serge、Ramalingam Murugan、Bae Hojae、Orive Gorka、Fujie Toshinori、Hori Takeshi、Nashimoto Yuji、Shi Xuetao、Kaji Hirokazu
    • Journal Title

      Sensors

      Volume: 23 Issue: 12 Pages: 5625-5625

    • DOI

      10.3390/s23125625

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oxygen metabolism analysis of a single organoid for non-invasive discrimination of cancer subpopulations with different growth capabilities2023

    • Author(s)
      Nashimoto Yuji、Shishido Shotaro、Onuma Kunishige、Ino Kosuke、Inoue Masahiro、Shiku Hitoshi
    • Journal Title

      Frontiers in Bioengineering and Biotechnology

      Volume: 11 Pages: 1184325-1184325

    • DOI

      10.3389/fbioe.2023.1184325

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Minimally Invasive Sub-Retinal Transplantation of RPE-J Cells on a Biodegradable Composite PCL/Collagen Nanosheet2023

    • Author(s)
      Yamashita Kazuya、Ostrovidov Serge、Raut Bibek、Hori Takeshi、Nashimoto Yuji、Nagai Nobuhiro、Abe Toshiaki、Kaji Hirokazu
    • Journal Title

      Cell Transplantation

      Volume: 32 Pages: 1-16

    • DOI

      10.1177/09636897231165117

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Topographical evaluation of human mesenchymal stem cells during osteogenic differentiation using scanning ion conductance microscopy2023

    • Author(s)
      Nozawa Kota、Zhang Xuyang、Nakamura Takuo、Nashimoto Yuji、Takahashi Yasufumi、Ino Kosuke、Shiku Hitoshi
    • Journal Title

      Electrochimica Acta

      Volume: 449 Pages: 142192-142192

    • DOI

      10.1016/j.electacta.2023.142192

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pericytes and shear stress each alter the shape of a self-assembled vascular network2023

    • Author(s)
      Kazuya Fujimoto, Scott Erickson, Masamune Nakayama, Hiroki Ihara, Kei Sugihara, Yuji Nashimoto, Koichi Nishiyama, Takashi Miura, Ryuji Yokokawa
    • Journal Title

      Lab on a chip

      Volume: 23 Issue: 2 Pages: 306-306

    • DOI

      10.1039/d2lc00605g

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Electrochemical sensing of oxygen metabolism for a three-dimensional cultured model with biomimetic vascular flow2023

    • Author(s)
      Nashimoto Yuji、Mukomoto Rei、Imaizumi Takuto、Terai Takato、Shishido Shotaro、Ino Kosuke、Yokokawa Ryuji、Miura Takashi、Onuma Kunishige、Inoue Masahiro、Shiku Hitoshi
    • Journal Title

      Biosensors and Bioelectronics

      Volume: 219 Pages: 114808-114808

    • DOI

      10.1016/j.bios.2022.114808

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Electrochemiluminescence Imaging Based on Bipolar Electrochemistry Using Commercially Available Anisotropic Conductive Films2022

    • Author(s)
      Akasaka Rise、Ino Kosuke、Iwama Tomoki、Inoue Kumi Y.、Nashimoto Yuji、Shiku Hitoshi
    • Journal Title

      Sensors and Materials

      Volume: 34 Issue: 8 Pages: 3113

    • DOI

      10.18494/SAM3745

    • ISSN
      0914-4935, 2435-0869
    • Year and Date
      2022-08-15
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Electrochemical microwell sensor with Fe-N co-doped carbon catalyst to monitor nitric oxide release from endothelial cell spheroids2022

    • Author(s)
      Hiramoto Kaoru、Iwase Kazuyuki、Utagawa Yoshinobu、Nashimoto Yuji、Honma Itaru、Ino Kosuke、Shiku Hitoshi
    • Journal Title

      Analytical Sciences

      Volume: 38 Issue: 10 Pages: 1297-1304

    • DOI

      10.1007/s44211-022-00160-0

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Electrochemiluminescence imaging of cellular adhesion in vascular endothelial cells during tube formation on hydrogel scaffolds2022

    • Author(s)
      Ino Kosuke、Komatsu Keika、Hiramoto Kaoru、Utagawa Yoshinobu、Nashimoto Yuji、Shiku Hitoshi
    • Journal Title

      Electrochimica Acta

      Volume: 415 Pages: 140240-140240

    • DOI

      10.1016/j.electacta.2022.140240

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Electrochemical Glue for Binding Chitosan?Alginate Hydrogel Fibers for Cell Culture2022

    • Author(s)
      Utagawa Yoshinobu、Ino Kosuke、Kumagai Tatsuki、Hiramoto Kaoru、Takinoue Masahiro、Nashimoto Yuji、Shiku Hitoshi
    • Journal Title

      Micromachines

      Volume: 13 Issue: 3 Pages: 420-420

    • DOI

      10.3390/mi13030420

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 生体模倣システムを用いたがん微小環境モデル内の血管網の作出と介入2023

    • Author(s)
      梨本裕司
    • Organizer
      第97回薬理学会年会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 走査型イオンコンダクタンス顕微鏡による細胞の超精密穿刺と内容物分取2023

    • Author(s)
      梨本裕司、堀武史、梶弘和
    • Organizer
      第32回日本コンピューター外科学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 血管を場とする生体内現象の模倣とその評価システムの作出2023

    • Author(s)
      梨本裕司
    • Organizer
      日本動物実験代替法学会 第36回大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 生体模倣デバイスを用いたがん転移におけるがん微小環境の影響の評価2023

    • Author(s)
      梨本裕司
    • Organizer
      日本動物実験代替法学会 第36回大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 歯肉組織への細菌の浸潤観察を目的とした歯肉上皮および歯肉血管網の模倣2023

    • Author(s)
      佐藤 優輝、梨本 裕司、大杉 勇人、堀 武志、吉田 昭太郎、片桐 さやか、梶 弘和
    • Organizer
      日本動物実験代替法学会 第36回大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] インサートカラム型血管網 MPSの開発2023

    • Author(s)
      堀 武志、安藤 萌、山本 茜、北野 勇、石原 甲平、水田 太郎、吉田 昭太郎、梨本 裕司、梶 弘和
    • Organizer
      日本動物実験代替法学会 第36回大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ヒト胎盤オルガノイドの作製と病原体曝露の影響の解析2023

    • Author(s)
      JIANG BIN、堀武志、岡江寛明、大杉勇人、片桐さやか、梨本裕司、有馬隆博、梶弘和
    • Organizer
      化学とマイクロ・ナノシステム学会第48回研究会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 歯周病原細菌の浸潤評価に向けた3D歯肉上皮モデルの作製2023

    • Author(s)
      柴田蒼大、佐藤優輝、梨本裕司、大杉勇人、堀武志、片桐さやか、梶弘和
    • Organizer
      化学とマイクロ・ナノシステム学会第48回研究会
    • Related Report
      2023 Annual Research Report
  • [Presentation] マイクロ流体デバイスを用いたヒト胎盤モデルにおける灌流依存的細胞分化の解析2023

    • Author(s)
      リージアユンライアン、堀武志、岡江寛明、梨本裕司、有馬隆博、梶弘和
    • Organizer
      化学とマイクロ・ナノシステム学会第48回研究会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 内皮間葉移行on-a-chip確立に向けた形態・分子生物学的パラメータの解析2023

    • Author(s)
      土屋香碧、梨本裕司、堀武志、吉田昭太郎、高橋和樹、渡部徹郎、梶弘和
    • Organizer
      化学とマイクロ・ナノシステム学会第48回研究会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 灌流可能な人工血管網を作製するためのカラム型デバイスの開発2023

    • Author(s)
      安藤萌、堀武志、山本茜、北野勇、石原甲平、水田太郎、吉田昭太郎、梨本裕司、梶弘和
    • Organizer
      化学とマイクロ・ナノシステム学会第48回研究会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 細胞培養肉作製に向けたバイオマスメッシュシートの開発2023

    • Author(s)
      許家誠、堀武志、梨本裕司、吉田昭太郎、梶弘和
    • Organizer
      化学とマイクロ・ナノシステム学会第48回研究会
    • Related Report
      2023 Annual Research Report
  • [Presentation] マイクロ流体デバイスによる血管を備えるがん環境の再現とその電気化学計測システムの作出2023

    • Author(s)
      梨本裕司
    • Organizer
      有機機能材料のリソグラフィ加工コンソーシアム
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 血流を備える生体模倣システムの作出と探針型デバイスによる「その場」センシング2023

    • Author(s)
      梨本裕司
    • Organizer
      日本薬物動態学会第38回年会/第23回シトクロムP450国際会議国際合同大会
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ?査型電気化学顕微鏡を?いたがんオルガノイドの?侵襲的な増殖能の識別2023

    • Author(s)
      梨本 裕司、宍? 昌太郎、小沼 邦重、伊野 浩介、井上 正宏、珠玖 仁
    • Organizer
      日本分析化学会第72年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] マイクロ流体デバイスを用いた 単一膵島の血管形成能力の評価2023

    • Author(s)
      梨本 裕司、今野 杏、今泉 拓斗、西川 香里、伊野 浩介、堀 武志、梶 弘和、新宅 博文、後藤 昌史、珠玖 仁
    • Organizer
      日本分析化学会第72年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Real-time monitoring of the effects of vasculature in a tumor microenvironment2023

    • Author(s)
      Yuji Nashimoto、Kao Tsuchiya、Kazuki Takahashi、Takeshi Hori、Serge Ostrovidov、Shotaro Yoshida、Tetsuo Watabe、Hirokazu Kaji
    • Organizer
      MPS World Summit 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 内皮間葉移行を可視化する血管網プラットフォームの構築2023

    • Author(s)
      土屋香碧、梨本裕司、堀武志、吉田昭太郎、高橋和樹、渡部徹郎、梶弘和
    • Organizer
      日本機械学会 第35回バイオエンジニアリグ講演会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Development of a biomass mesh sheet for cell-cultured meat2023

    • Author(s)
      許家誠、堀武志、梨本裕司、吉田昭太郎、梶弘和
    • Organizer
      化学とマイクロ・ナノシステム学会第47回研究会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 網膜における異常血管新生の模倣に向けたマイクロ流体デバイスの開発2023

    • Author(s)
      稲垣皓介、堀武志、梨本裕司、吉田昭太郎、梶弘和
    • Organizer
      化学とマイクロ・ナノシステム学会第47回研究会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 歯周病原細菌の血管浸潤を可視化するプラットフォームの構築2023

    • Author(s)
      佐藤優輝、梨本裕司、大杉勇人、堀武志、吉田昭太郎、片桐さやか、梶弘和
    • Organizer
      化学とマイクロ・ナノシステム学会 第47 回研究会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 生体模倣システムを用いたがん周 囲の血管網再構築と「その場」酸 素消費量計測2022

    • Author(s)
      梨本裕司,向本励,今泉拓斗,寺井崇人,宍戸昌太郎,伊野浩介,横川隆司,三浦岳,小沼邦重,井上正宏,珠玖仁
    • Organizer
      第18回 がんとハイポキシア研究会 in 桐生
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
  • [Presentation] 患者由来がん細胞凝集塊の電気化学測定による 酸素消費量の不均一性の評価2022

    • Author(s)
      宍戸昌太郎,梨本裕司,伊野浩介,小沼邦重,井上正宏,珠玖仁
    • Organizer
      第18回 がんとハイポキシア研究会 in 桐生
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
  • [Presentation] 探針型デバイスによる電気化学的 バイオセンシングの生体模倣システムへの展開2022

    • Author(s)
      梨本裕司
    • Organizer
      センサ&IoTコンソーシアム 公開シンポジウム2022
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Invited
  • [Presentation] 多孔電極を用いた細胞代謝物のin situ リアルタイム計測2022

    • Author(s)
      宇田川喜信,伊野浩介,梨本裕司,珠玖仁
    • Organizer
      化学とマイクロ・ナノシステム学会第46回研究会
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
  • [Presentation] マイクロメッシュシートを利用した三次元細胞培養法の開発2022

    • Author(s)
      安藤萌,堀武志,山本茜,北野勇,石原甲平,水田太郎,長濱宏治,吉田昭太郎,梨本裕司,梶弘和
    • Organizer
      化学とマイクロ・ナノシステム学会第46回研究会
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
  • [Presentation] 血管網デバイスを用いた内皮間葉移行および口腔癌の転移メカニズムの解明2022

    • Author(s)
      土屋香碧,梨本裕司,堀武志,吉田昭太郎,高橋和樹,渡部徹郎,梶弘和
    • Organizer
      化学とマイクロ・ナノシステム学会第46回研究会
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
  • [Presentation] 血管網を備えたがんモデルの構築と その評価システムの開発2022

    • Author(s)
      梨本裕司
    • Organizer
      第8回細胞凝集研究会
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Invited
  • [Presentation] Electrochemical Analysis of Vasculature-on-a-Chip and Vascularized-3D-Model-on-a-Chip2022

    • Author(s)
      Yuji Nashimoto
    • Organizer
      3D-Bioprinting, Biofabrication, Organoids & Organs-on-Chips Asia 2022
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Engineering and analyzing organ microenvironment with a perfusable vascular network and its application in oral pathology2022

    • Author(s)
      Yuji Nashimoto,Yuki Sato,Takeshi Hori,Kosuke Ino,Hitoshi Shiku,Sayaka Katagiri,Hirokazu Kaji
    • Organizer
      Interface Summer Seminar 2022
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Electrochemical analysis of a respiration activity for a three-dimensional cultured model with biomimetic vascular flow2022

    • Author(s)
      Yuji Nashimoto,Rei Mukomoto,Takuto Imaizumi,Kosuke Ino,Hitoshi Shiku
    • Organizer
      9th World Congress of Biomechanics
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2025-01-30  

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