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Tissue engineering for vascularization based on flow regulation

Research Project

Project/Area Number 16H03173
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionKeio University

Principal Investigator

SUDO RYO  慶應義塾大学, 理工学部(矢上), 准教授 (20407141)

Co-Investigator(Kenkyū-buntansha) 谷下 一夫  慶應義塾大学, 理工学部(矢上), 名誉教授 (10101776)
三高 俊広  札幌医科大学, 医学部, 教授 (50231618)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2016: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords血管化 / マイクロ流体デバイス / 肝臓 / 血管 / 組織工学 / 生物・生体工学 / マイクロ・ナノデバイス / 再生医学
Outline of Final Research Achievements

In the field of tissue engineering, it is desired to introduce capillaries into reconstructed three-dimensional (3D) tissues in vitro, which is called vascularization. In this study, we investigated vascularization of tissue-engineered constructs by using microfluidic devices and gel microbeads. Our results demonstrated that the size of gel microbeads was important for tissue organization of hepatocytes while the effect of gel microbeads on vascularization was limited. In addition, we found that mesenchymal stem cells not only contributed to the stabilization of capillary networks but also promoted vascularization of tissue-engineered constructs.

Academic Significance and Societal Importance of the Research Achievements

生体外で組織や臓器を再生しようとする組織工学の分野では、血管網を含む三次元組織の再生が実現していない。そこで、細胞から三次元組織を構築し、血管を導入する血管化の手法を確立することが大きな課題になっている。本研究では、マイクロ流体デバイスを用いて細胞周囲の流れの環境を制御するとともに、ゲルビーズを導入することで血管化組織の構築手法を検討した。研究結果より血管化組織を再生するために必要な因子が明らかになり、血管化組織の再生手法の確立に貢献する点に学術的かつ社会的な意義がある。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (45 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (7 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (32 results) (of which Int'l Joint Research: 11 results,  Invited: 8 results) Book (3 results) Remarks (1 results)

  • [Int'l Joint Research] Harvard University/Massachusetts Institute of Technology(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Korea University(韓国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Comparison of organ-specific endothelial cells in terms of microvascular formation and endothelial barrier functions2019

    • Author(s)
      Uwamori Hiroyuki、Ono Yuuichi、Yamashita Tadahiro、Arai Ken、Sudo Ryo
    • Journal Title

      Microvascular Research

      Volume: 122 Pages: 60-70

    • DOI

      10.1016/j.mvr.2018.11.007

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Construction of Continuous Capillary Networks Stabilized by Pericyte-like Perivascular Cells2019

    • Author(s)
      Kyoko Yamamoto, Kohei Tanimura, Masafumi Watanabe, Hiromu Sano, Hiroyuki Uwamori, Yo Mabuchi, Yumi Matsuzaki, Seok Chung, Roger D. Kamm, Kazuo Tanishita, Ryo Sudo
    • Journal Title

      Tissue Engineering Part A

      Volume: 25 Issue: 5-6 Pages: 499-510

    • DOI

      10.1089/ten.tea.2018.0186

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Construction of sinusoid-scale microvessels in perfusion culture of a decellularized liver2019

    • Author(s)
      Masafumi Watanabe, Koki Yano, Koki Okawa, Tadahiro Yamashita, Kazuki Tajima, Kazuaki Sawada, Hiroshi Yagi, Yuko Kitagawa, Kazuo Tanishita, Ryo Sudo
    • Journal Title

      Acta Biomaterialia

      Volume: 印刷中 Pages: 30767-0

    • DOI

      10.1016/j.actbio.2018.12.042

    • NAID

      130007637470

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of an <i>in vitro</i> vascular anastomosis model in a microfluidic device2019

    • Author(s)
      Masafumi Watanabe, Ryo Sudo
    • Journal Title

      Journal of Biomechanical Science and Engineering

      Volume: 14 Issue: 3 Pages: 18-00521-18-00521

    • DOI

      10.1299/jbse.18-00521

    • NAID

      130007741719

    • ISSN
      1880-9863
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Self-organization of hepatocyte morphogenesis depending on the size of collagen microbeads relative to hepatocytes2019

    • Author(s)
      Mohammad Ajoudanian, Keita Enomoto, Yasuaki Tokunaga, Hiroshi Minami, Seok Chung, Kazuo Tanishita, Roger D. Kamm, Ryo Sudo
    • Journal Title

      Biofabrication

      Volume: 印刷中

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Reconstruction of Hepatic Tissue Structures Using Interstitial Flow in a Microfluidic Device2018

    • Author(s)
      Ryo Sudo
    • Journal Title

      Methods in Molecular Biology

      Volume: 1905 Pages: 167-174

    • DOI

      10.1007/978-1-4939-8961-4_15

    • ISBN
      9781493989607, 9781493989614
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fabrication of type I collagen microcarrier using a microfluidic 3D T-junction device and its application for the quantitative analysis of cell-ECM interactions2016

    • Author(s)
      Junghyo Yoon, Jaehoon Kim, Hyo Eun Jeong, Ryo Sudo, Myung-Jin Park, Seok Chung
    • Journal Title

      Biofabrication

      Volume: 8 Issue: 3 Pages: 035014-035014

    • DOI

      10.1088/1758-5090/8/3/035014

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] In vitro tissue engineering using 3D microfluidic devices2019

    • Author(s)
      Ryo Sudo
    • Organizer
      International Symposium on SSS Laser Processing
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Regeneration of organ-scale vascular networks in a decellularized liver by flow-induced mechanical stress2019

    • Author(s)
      Masafumi Watanabe, Koki Yano, Koki Okawa, Ryo Sudo
    • Organizer
      International Symposium on SSS Laser Processing
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Flow-induced mechanical force promotes microvascular formation in a decellularized liver2019

    • Author(s)
      Masafumi Watanabe, Koki Yano, Koki Okawa, Tadahiro Yamashita, Ryo Sudo
    • Organizer
      3rd International Symposium on Nanoarchitectonics for Mechanobiology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analysis of morphology and function of cholangiocytes cultured on soft and rigid substrates2019

    • Author(s)
      Ryota Kaku, Yasuaki Tokunaga, Ryo Sudo
    • Organizer
      3rd International Symposium on Nanoarchitectonics for Mechanobiology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 微小血管網と三次元肝細胞組織を組み合わせた組織工学的手法2019

    • Author(s)
      須藤 亮
    • Organizer
      第18回 日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Investigation of microvessel morphological change and corresponding vascular wall shear stress distribution during in vitro vascular remodeling in a microfluidic device2018

    • Author(s)
      Masafumi Watanabe, Ryosuke Murai, Ryo Sudo
    • Organizer
      World Congress of Biomechanics 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Microfluidic-based application of an in vitro microvessel model: investigation of vascular morphology and corresponding wall shear stress during vascular remodeling2018

    • Author(s)
      Masafumi Watanabe, Ryosuke Murai, Ryo Sudo
    • Organizer
      Lab-on-a-Chip and Microfluidics World Congress 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脱細胞化肝臓骨格の還流培養における類洞スケールの毛細血管構造の構築2018

    • Author(s)
      渡邉應文、矢野公規、大川航輝、谷下一夫、須藤亮
    • Organizer
      日本機械学会 第29回バイオフロンティア講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Construction of in vitro hierarchical vascular networks using tissue-derived microchannels of a decellularized liver scaffold2018

    • Author(s)
      Masafumi Watanabe, Koki Yano, Koki Okawa, Ryo Sudo
    • Organizer
      EMBS Micro and Nanotechnology in Medicine Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マイクロ流体デバイスを用いた血管化肝組織の構築2018

    • Author(s)
      保谷高明、須藤亮
    • Organizer
      日本機械学会 第31回バイオエンジニアリング講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マイクロ流体デバイスを用いた流れによる血管リモデリング2018

    • Author(s)
      佐野紘夢、大野航平、渡邉應文、須藤亮
    • Organizer
      日本機械学会 第31回バイオエンジニアリング講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 肝スフェロイドと血管の相互作用調査のための培養モデル2018

    • Author(s)
      大川航輝、三場詩織、須藤亮
    • Organizer
      日本機械学会 第31回バイオエンジニアリング講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マイクロ培養プラットフォームを用いた三次元組織形成と細胞診断2018

    • Author(s)
      須藤亮
    • Organizer
      第20回 日本医工ものづくりコモンズシンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 微小培養環境制御に基づく3次元組織工学と細胞バイオメカニクス2017

    • Author(s)
      須藤 亮
    • Organizer
      次世代バイオ・医療技術研究会
    • Place of Presentation
      東京大学生産技術研究所(東京都・目黒区)
    • Year and Date
      2017-03-31
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Multiscale tissue engineering for liver reconstruction2017

    • Author(s)
      Ryo Sudo
    • Organizer
      1st International Symposium on Applied Abstraction and Integrated Design (AAID2017)
    • Place of Presentation
      慶應義塾大学日吉キャンパス来往舎(神奈川県・横浜市)
    • Year and Date
      2017-03-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] 肝細胞調製培養液を用いた血管化肝組織構築のための工学的アプローチ2017

    • Author(s)
      徳永康明、南拓志、須藤亮
    • Organizer
      シンポジウム:細胞アッセイ技術の現状と将来
    • Place of Presentation
      東京大学生産技術研究所コンベンションホール(東京都・目黒区)
    • Year and Date
      2017-01-31
    • Related Report
      2016 Annual Research Report
  • [Presentation] 血管内皮細胞-間葉系幹細胞3次元共培養モデルにおける血管リモデリングの調査2017

    • Author(s)
      村居良祐、佐野紘夢、須藤亮
    • Organizer
      日本機械学会 第29回バイオエンジニアリング講演会
    • Place of Presentation
      愛知県産業労働センター ウインクあいち(愛知県・名古屋市)
    • Year and Date
      2017-01-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] 血管内皮細胞と間葉系幹細胞の共培養による脱細胞化肝臓内の血管ネットワークの再構築2017

    • Author(s)
      渡邉應文、矢野公規、大川航輝、須藤亮
    • Organizer
      日本機械学会 第29回バイオエンジニアリング講演会
    • Place of Presentation
      愛知県産業労働センター ウインクあいち(愛知県・名古屋市)
    • Year and Date
      2017-01-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] 肝細胞-コラーゲンマイクロゲルビーズ混成組織の血管化に向けた検討2017

    • Author(s)
      南拓志、保谷高明、須藤亮
    • Organizer
      日本機械学会 第29回バイオエンジニアリング講演会
    • Place of Presentation
      愛知県産業労働センター ウインクあいち(愛知県・名古屋市)
    • Year and Date
      2017-01-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] Reconstruction of vascular networks in perfusion culture using a decellularized liver scaffold2017

    • Author(s)
      Koki Yano, Koki Okawa, Masafumi Watanabe, Ryo Sudo
    • Organizer
      TERMIS (Tissue Engineering and Regenerative Medicine International Society) European Chapter Meeting 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] システムデザイン工学に基づく3次元組織工学2017

    • Author(s)
      須藤亮
    • Organizer
      慶應ライフサイエンスシンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Self-organization of hepatocyte morphogenesis depending on the size of collagen microbeads2017

    • Author(s)
      Ryo Sudo, Keita Enomoto, Mohammad Ajoudanian, Yasuaki Tokunaga, Hiroshi Minami
    • Organizer
      5th Switzerland-Japan Workshop on Biomechanics SJB 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] マイクロ流体デバイスを用いた血管リモデリングにおける間質流の影響2017

    • Author(s)
      佐野紘夢、村居良祐、須藤亮
    • Organizer
      日本機械学会 第28回バイオフロンティア講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Bioengineering approaches to the 3D tissue engineering2017

    • Author(s)
      Ryo Sudo
    • Organizer
      The first joint conference on sophisticated coupling and integration of genius kernel technologies in Grenoble and Keio
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マイクロ流体デバイスを用いた三次元肝組織構築の取り組み2017

    • Author(s)
      須藤亮
    • Organizer
      日本薬物動態学会第32回年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Effect of interstitial flow on vascular remodeling in a microfluidic device2017

    • Author(s)
      Hiromu Sano, Ryo Sudo
    • Organizer
      3rd International Symposium on Mechanobiology
    • Related Report
      2017 Annual Research Report
  • [Presentation] バイオエンジニアリングに基づく3次元組織工学2017

    • Author(s)
      須藤亮
    • Organizer
      日本機械学会 第30回バイオエンジニアリング講演会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] コラーゲンサンドイッチ培養を用いた胆管形成への試み2017

    • Author(s)
      徳永康明、須藤亮
    • Organizer
      日本機械学会 第30回バイオエンジニアリング講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脱細胞化肝臓骨格の還流培養による樹状血管網の再構築2017

    • Author(s)
      矢野公規、渡邉應文、大川航輝、須藤亮
    • Organizer
      日本機械学会 第30回バイオエンジニアリング講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脱細胞化肝臓骨格における血管ネットワーク再構築プロセスの観察2016

    • Author(s)
      矢野公規、渡邉應文、須藤亮
    • Organizer
      日本機械学会2016年度年次大会
    • Place of Presentation
      九州大学伊都キャンパス(福岡県・福岡市)
    • Year and Date
      2016-09-11
    • Related Report
      2016 Annual Research Report
  • [Presentation] Reconstruction of vascularized hepatocyte tissues by hepatocyte-conditioned medium in a microfluidic device2016

    • Author(s)
      Yasuaki Tokunaga, Hiroshi Minami, Ryo Sudo
    • Organizer
      38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)
    • Place of Presentation
      Orlando (USA)
    • Year and Date
      2016-08-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マイクロ流体デバイスにおける肝細胞調製培養液を使用した血管化肝組織構築の試み2016

    • Author(s)
      徳永康明、南拓志、須藤亮
    • Organizer
      第23回肝細胞研究会
    • Place of Presentation
      大阪大学中之島センター(大阪府・大阪市)
    • Year and Date
      2016-07-07
    • Related Report
      2016 Annual Research Report
  • [Book] 臓器チップの技術と開発動向(第7 章 マイクロ流体システムによる血管形成モデルと肝細胞3 次元培養モデルの融合)2018

    • Author(s)
      酒井康行、金森敏幸 監修 (須藤 亮 分担執筆)
    • Publisher
      シーエムシー出版
    • Related Report
      2018 Annual Research Report
  • [Book] 細胞のマルチスケールメカノバイオロジー2017

    • Author(s)
      佐藤 正明、安達 泰治、松下 慎二、井上 康博、平田 宏聡、曽我部 正博、出口 真次、安藤 譲二、山本 希美子、谷下 一夫、須藤 亮
    • Total Pages
      160
    • Publisher
      森北出版
    • ISBN
      9784627691414
    • Related Report
      2017 Annual Research Report
  • [Book] Vascular Engineering2016

    • Author(s)
      Ryo Sudo, Seok Chung, Yoojin Shin, Kazuo Tanishita (Editors: KazuoTanishita, Kimiko Yamamoto)
    • Total Pages
      401
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report
  • [Remarks] 慶應義塾大学理工学部システムデザイン工学科須藤研究室ホームページ

    • URL

      http://www.sudo.sd.keio.ac.jp/

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report 2016 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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