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2015 Fiscal Year Annual Research Report

肝臓等複雑化組織の構築と機能解明

Planned Research

Project AreaHyper Bio Assembler for 3D Celluler Innovation
Project/Area Number 23106009
Research InstitutionTokyo Women's Medical University

Principal Investigator

大和 雅之  東京女子医科大学, 医学部, 教授 (40267117)

Co-Investigator(Kenkyū-buntansha) 中山 正道  東京女子医科大学, 医学部, 講師 (00338980)
高橋 宏信  東京女子医科大学, 医学部, 助教 (00710039)
長瀬 健一  東京女子医科大学, 医学部, 講師 (10439838)
秋山 義勝  東京女子医科大学, 医学部, 講師 (20349640)
小林 純  東京女子医科大学, 医学部, 講師 (20385404)
Project Period (FY) 2011-04-01 – 2016-03-31
Keywords肝細胞シート / 成長因子 / 細胞シート工学 / 肝小葉 / 微細加工技術
Outline of Annual Research Achievements

肝臓の組織構造を構成する肝小葉類似構造を有する肝組織構築のためのバイオアセンブラ技術の包括的な研究および評価を行った。具体的には、以下の研究項目を実施した。(1) 生体組織を模倣した細胞シート工学による肝臓様組織の構築とその評価:成長因子を固定化した温度応答性細胞培養表面を用いて作製した肝実質細胞シートに血管内皮細胞シートを積層化し、肝組織としてのアルブミン産生能、肝特異的な遺伝子発現が長期にわたり維持されることを示した。(2)作製した3次元組織様構造体の in vitro および in vivo 評価:作製した肝細胞シートをコンフォーカル顕微鏡で観察し温度応答性細胞培養表面に固定化した成長因子が、肝細胞膜上に存在する膜レセプタータンパク質のリン酸化を引き起こしていることが示唆された。また、作製した肝細胞シートのラット皮下への移植実験を行い、短期間ではあるが移植した肝細胞シートが生着することを確認した。(3)班間連携A02班の関先生らのグループが開発した肝スフェロイドを包埋したコラーゲンゲルファイバーの機能と3次元組織様構造体作製への応用について評価を行った。また、竹内らのグループとは微細空間を有する中耳組織への細胞シートデバイスの設計および作製を行い、移植デバイスへの細胞シートの接着および移植デバイスからの細胞シート剥離を確認し、移植デバイスとしての有効性を検証した。岡嶋らのグループとは肝細胞の形状がアルブミン産生等の生理的な機能変化に相関がある点に着目し、共培養系における肝細胞のヤング率の変化を測定し、肝細胞を単独で培養した場合と血管内皮細胞との共培養を行った際の肝細胞の生理的な機能変化とヤング率変化の相関について評価を行った。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

  • Research Products

    (18 results)

All 2016 2015

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Acknowledgement Compliant: 5 results,  Open Access: 1 results) Presentation (12 results) (of which Int'l Joint Research: 12 results,  Invited: 5 results) Book (1 results)

  • [Journal Article] A heparin-modified thermoresponsive surface with heparin-binding epidermal growth factor like growth factor for maintaining hepatic functions in vitro and harvesting hepatocyte sheets2016

    • Author(s)
      Arisaka Y, Kobayashi J, Ohashi K, Tatsumi K, Kim K, Akiyama Y, Yamato M, Okano T
    • Journal Title

      Regenerative Therapy

      Volume: 3 Pages: 97-106

    • DOI

      10.1016/j.reth.2016.03.003

    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A Facile Method for Preparing Temperature-Responsive Cell Culture Surfaces by Using a Thioxanthone Photoinitiator Immobilized on a Polystyrene Surface2016

    • Author(s)
      Fukumori K, Akiyama Y, Yamato M and Okano T
    • Journal Title

      CHEMNANOMAT

      Volume: ND Pages: ND

    • DOI

      10.1002/cnma.201600056

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Cell sheet-based tissue engineering for organizing anisotropic tissue constructs produced using microfabricated thermoresponsive substrates2015

    • Author(s)
      Takahashi H and Okano T
    • Journal Title

      Advanced Healthcare Materials

      Volume: 4 Pages: 2388-2407

    • DOI

      10.1002/adhm.201500194

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Anisotropic cellular network formation in engineered muscle tissue through the self-organization of neurons and endothelial cells2015

    • Author(s)
      akahashi H, Shimizu T, Nakayama M, Yamato M, Okano T
    • Journal Title

      Advanced Healthcare Materials

      Volume: 4 Pages: 356-360

    • DOI

      10.1002/adhm.201400297

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Measurement of the dynamic behavior of thin poly(N-isopropylacrylamide) hydrogels and their phase transition temperatures measured using reflectometric interference spectroscopy2015

    • Author(s)
      Okada F, Akiyama Y, Kobayashi J, Ninomiya H, Kanazawa H, Yamato M, Okano T
    • Journal Title

      Journal of Nanoparticle Research

      Volume: 17 Pages: 148-154

    • DOI

      10.1007/s11051-015-2951-3

    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] A facile method for temperature-responsive cell culture surfaces by using thioxanthone photo-initiator immobilized polystyrene surfaces2016

    • Author(s)
      Akiyama Y
    • Organizer
      2016 EMN Bioinspired Materials Meeting
    • Place of Presentation
      Kaohsiung, Taipei
    • Year and Date
      2016-03-15
    • Int'l Joint Research / Invited
  • [Presentation] Nano-intelligent biomaterial surface for cell-sheets based tissue engineering2016

    • Author(s)
      Akiyama Y
    • Organizer
      BIT's 2nd Annual Waorld Congress of Smaart Materials-2106
    • Place of Presentation
      Singapore, Singapore
    • Year and Date
      2016-03-04
    • Int'l Joint Research / Invited
  • [Presentation] Fabrication of functional liver tissues by cell sheet-based bioassembler technologies2015

    • Author(s)
      Kobayashi J, Akiyama Y, Yamato M, Okano T
    • Organizer
      2015 International Symposium on Micro-NanoMechatronics and Human Science (MHS)
    • Place of Presentation
      Noyori Memorial Hall, Nagoya University, Nagoya
    • Year and Date
      2015-11-13
    • Int'l Joint Research
  • [Presentation] Stem Cell Separation using Thermoresponsive Copolymer Brushes having Cationic Charge2015

    • Author(s)
      Nagase K., Hatakeyama Y., Shimizu T., Matsuura K., Yamato M., Takeda N., Okano T
    • Organizer
      2015 International Symposium on Micro-NanoMechatronics and Human Science (MHS)
    • Place of Presentation
      Noyori Memorial Hall, Nagoya University, Nagoya
    • Year and Date
      2015-11-11
    • Int'l Joint Research
  • [Presentation] Creation of functional hepatocyte sheet tissues by using heparinized thermoresponsive surfaces2015

    • Author(s)
      Kobayashi J, Arisaka Y, Ohashi K, Tatsumi K, Kim K, Akiyama Y, Yamato M, Okano T
    • Organizer
      2015 4th TERMIS World Congress
    • Place of Presentation
      Boston, USA
    • Year and Date
      2015-09-09
    • Int'l Joint Research
  • [Presentation] Alternation of PIPAAm Modified PDMS Surface Properties Induced by Mechanical Stretching Stress2015

    • Author(s)
      Akiyama Y, Matsuyama M, Yamato M, Takeda N, Okano T
    • Organizer
      11th International Symposium on Frontiers in Biomedical Polymers
    • Place of Presentation
      Riva del Garda, Italy
    • Year and Date
      2015-07-09
    • Int'l Joint Research
  • [Presentation] Heparin-functionalized thermoresponsive cell culture surfaces for creation of functional hepatic tissues2015

    • Author(s)
      Kobayashi J, Arisaka Y, Ohashi K, Tatsumi K, Kim K, Akiyama Y, Yamato M, Okano T
    • Organizer
      International Symposium on Frontiers in Biomedical Polymers
    • Place of Presentation
      Riva del Garda, Italy
    • Year and Date
      2015-07-09
    • Int'l Joint Research
  • [Presentation] Creation of functional liver tissues by cell-sheet technologies2015

    • Author(s)
      Kobayashi J
    • Organizer
      IEEE Robotics and Automaton Society (ICRA) 2015 Workshop “Hyper Bio Assembler for 3D Cellular System Innovation”
    • Place of Presentation
      Seattle, USA
    • Year and Date
      2015-05-30
    • Int'l Joint Research / Invited
  • [Presentation] Recent development of poly(N-isopropylacrylamide) based temperature-responsive cell culture surface2015

    • Author(s)
      Akiyama Y
    • Organizer
      2015 E-MRS Spring Meeting
    • Place of Presentation
      Lille, France
    • Year and Date
      2015-05-12
    • Int'l Joint Research / Invited
  • [Presentation] fficient fabrication of hepatocyte cells sheet with heparin-immobilized temperature-responsive cell culture surfaces2015

    • Author(s)
      Akiyama Y, Kobayashi J, Arisaka Y, Yamato M, Okano T
    • Organizer
      2015 E-MRS Spring Meeting
    • Place of Presentation
      Lille, France
    • Year and Date
      2015-05-12
    • Int'l Joint Research / Invited
  • [Presentation] Surface design of heparin-functionalized thermoresponsive cell culture substrates for maintaining hepatic functions and harvesting cultured hepatocyte sheets2015

    • Author(s)
      Kobayashi J, Arisaka Y, Ohashi K, Tatsumi K, Kim K, Akiyama Y, Yamato M, Okano T
    • Organizer
      Society For Biomaterials 2015 Annual Meeting and Exposition
    • Place of Presentation
      Charlotte, USA
    • Year and Date
      2015-04-17
    • Int'l Joint Research
  • [Presentation] Light-sensitive Fluoropolymer Coated Surface for Control of Cell Adhesion Behavior2015

    • Author(s)
      Nakayama M, Kanno T, Kikuchi A, and Okano T
    • Organizer
      Society for Biomaterials 2015 Annual Meeting & Exposition (SFB2015)
    • Place of Presentation
      Charlotte, USA
    • Year and Date
      2015-04-16
    • Int'l Joint Research
  • [Book] Hyper Bio Assembler for 3D Cellular Systems2015

    • Author(s)
      FUKUMORI Kazuhiro, TAKAHASHI Hironobu, KOBAYASHI Jun, NAKAYAMA Masamichi, AKIYAMA Yoshikatsu, YAMATO Masayuki
    • Total Pages
      349
    • Publisher
      Springer

URL: 

Published: 2017-01-06  

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