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免疫抑制剤の不要な移植を目指した患者由来細胞と膵島の3次元複合体の創製

Publicly

Project AreaHyper Bio Assembler for 3D Celluler Innovation
Project/Area Number 26106709
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Science and Engineering
Research InstitutionThe University of Tokyo

Principal Investigator

寺村 裕治  東京大学, 工学(系)研究科(研究院), 准教授 (10365421)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2015: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywords膵島移植 / PEG脂質 / 糖尿病 / 細胞移植 / DNA
Outline of Annual Research Achievements

本研究では、レシピエント由来の細胞を利用して、細胞により膵ランゲルハンス島(膵島)の表面をカプセル化し、異種細胞との3次元複合体を構築して、移植後の免疫拒絶反応を抑制できる生体適合性の高いバイオ人工膵臓の開発が目的である。両親倍性高分子であるポリエチレングリコール結合脂質(PEG脂質)誘導体を利用して、膵島表面に異種細胞である血管内皮細胞や線維芽細胞などの様々な細胞を固定化し、異種細胞から構成される3次元複合体の構築手法の確立を目指す。
本研究では、親水性高分子であるPEGと長鎖疎水部を有するPEG脂質の末端に、相補的なDNA(polyA20とpolyT20)を導入して、膵島表面と固定化した細胞表面へ導入して、DNA同士のハイブリダイザーションによって細胞と膵島の接着を誘導して、複合体の形成を試みたところ、すべての細胞種において、膵島表面への固定化が可能であることが分かった。また、 接着誘導ペプチドであるRGDを、PEG脂質を用いて膵島表面へ導入することで、固定化した細胞が膵島内部へ移動する現象が見られ、3次元複合体の構築へ大きく影響を与えることが分かった。

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。

Report

(2 results)
  • 2015 Annual Research Report
  • 2014 Annual Research Report

Research Products

(25 results)

All 2015 2014 Other

All Int'l Joint Research Journal Article Presentation Patent(Industrial Property Rights)

  • [Int'l Joint Research] ウプサラ大学/リンネア大学(スウェーデン)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] オスロ大学/トロムソ大学(ノルウェー)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] ウプサラ大学/リンネア大学/カロリンスカ研究所(スウェーデン)

    • Related Report
      2014 Annual Research Report
  • [Int'l Joint Research] オスロ大学(ノルウェー)

    • Related Report
      2014 Annual Research Report
  • [Int'l Joint Research] カールスルーエ工科大学(ドイツ)

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Stable surface coating of silicone elastomer with phosphorylcholineand organosilane copolymer with cross-linking for repelling proteins2015

    • Author(s)
      Koji Nagahashi, Yuji Teramura, Madoka Takai
    • Journal Title

      Colloids and Surfaces B: Biointerfaces

      Volume: 94 Pages: 384-391

    • DOI
      10.1016/j.colsurfb.2015.07.040
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Cell surface modification with ssDNA-PEG-lipid for analysing intercellular interactions between different cells2015

    • Author(s)
      Yuji Teramura
    • Journal Title

      Biomaterials

      Volume: 48 Pages: 119-128

    • DOI
      10.1016/j.biomaterials.2015.01.032
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma2015

    • Author(s)
      Anna E. Engberg, Per H. Nilsson, Shan Huang, Karin Fromell, Osama A Hamad, Tom Eirik Mollnes, Jenny P. Rosengren-Holmberg, Kerstin Sandholm, Yuji Teramura, Ian A. Nicholls, Bo Nilsson, Kristina N. Ekdahl
    • Journal Title

      Biomaterials

      Volume: 36 Pages: 55-65

    • DOI
      10.1016/j.biomaterials.2014.09.011
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cell surface engineering for regulation of immune reactions in cell transplantation2015

    • Author(s)
      Yuji Teramura, Sana Asif, Kristina, N, Ekdahl, Bo Nilsson
    • Journal Title

      Adv Exp Med Biol

      Volume: 865 Pages: 189-209

    • DOI
      10.1007/978-3-319-18603-0_12
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Thromboinflammation in Therapeutic Medicine2015

    • Author(s)
      Kristina, N, Ekdahl, Yuji Teramura, Sana Asif, Nina Jonsson, Peetra, U, Magnusson, Bo Nilsson
    • Journal Title

      Adv Exp Med Biol

      Volume: 865 Pages: 3-17

    • DOI
      10.1007/978-3-319-18603-0_1
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Transplantation of Co-aggregates of Sertoli cells and Islet cells into Liver Without Immunosuppression2014

    • Author(s)
      Naohiro Takemoto, Xibao Liu, Kento Takii, Yuji Teramura, and Hiroo Iwata
    • Journal Title

      Transplantation

      Volume: 97 Pages: 287-293

    • DOI
      10.1097/01.tp.0000438198.76531.03
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Do ABO Blood Group Antigens Hamper the Therapeutic Efficacy of Mesenchymal Stromal Cells?2014

    • Author(s)
      Guido Moll, Annika Hult, Lena von Bahr, Jessica J. Alm, Nina Heldring, Osama A. Hamad, Lillemor Stenbeck-Funke, Stella Larsson, Yuji Teramura, Helene Roelofs, Bo Nilsson, Willem E. Fibbe, Martin L. Olsson, Katarina Le Blanc
    • Journal Title

      PLoS ONE

      Volume: 9

    • DOI
      10.1371/journal.pone.0085040
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mediation of a non-proteolytic activation of complement component C3 by phospholipid vesicles2014

    • Author(s)
      Yvonne Klapper, Osama A Hamad, Yuji Teramura, Gero Leneweit, Gerd Ulrich Nienhaus, Daniel Ricklin, John D. Lambris, Kristina N Ekdahl, Bo Nilsson
    • Journal Title

      Biomaterials

      Volume: 35 Pages: 3688-3696

    • DOI
      10.1016/j.biomaterials.2013.12.085
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Lectin-tagged Fluorescent Polymeric Nanoparticles for Targeting of Sialic Acid on the Living Cells2014

    • Author(s)
      Jaebum Cho, Keiichiro Kushiro, Yuji Teramura, Madoka Takai
    • Journal Title

      Biomacromolecules

      Volume: 15 Pages: 2012-2018

    • DOI
      10.1021/bm500159r
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Do cryopreserved mesenchymal stromal cells display impaired immunomodulatory and therapeutic properties?2014

    • Author(s)
      Guido Moll, Lena von Bahr, Jessica J. Alm, Lindsay C. Davies, Nina Heldring, Lillemor Stenbeck-Funke, Osama A. Hamad, Robin Hinsch, Lech Ignatowicz, Matthew Locke, Helena Lonnies, John D. Lambris, Yuji Teramura, Kristina Nilsson-Ekdahl, Bo Nilsson, Katarina Le Blanc
    • Journal Title

      Stem Cells

      Volume: 32 Pages: 2430-2442

    • DOI
      10.1002/stem.1729
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Heparinzation of cell surface with heparin-binding peptide-conjugated PEG-lipid for regulating thromboinflammation in cell transplantation of human MSC and hepatocyte2015

    • Author(s)
      Yuji Teramura, Sana Asif, Kristina Nilsson-Ekdahl, Bo Nilsson
    • Organizer
      IPITA-IXA-CTS 2015
    • Place of Presentation
      メルボルン、オーストラリア
    • Year and Date
      2015-11-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PEG脂質による血管内皮細胞の表面修飾とブタ腎移植の虚血再灌流障害への保護効果2015

    • Author(s)
      寺村裕治、Sana Asif , Kristina Nilsson-Ekdahl, Bo Nilsson, Alireza Biglarnia
    • Organizer
      第37回日本バイオマテリアル学会
    • Place of Presentation
      京都府京都市南区 京都テルサ
    • Year and Date
      2015-11-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] 細胞同士の相互作用を調べるための高分子細胞表面修飾剤2015

    • Author(s)
      寺村裕治
    • Organizer
      第64回高分子討論会
    • Place of Presentation
      宮城県仙台市 東北大学川内キャンパス
    • Year and Date
      2015-09-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヒト膵島表面への抗凝固活性を有するrCD39の固定化 と細胞傷害抑制効果2015

    • Author(s)
      寺村裕治、Sana Asif , Kristina Nilsson-Ekdahl, Bo Nilsson
    • Organizer
      第44回医用高分子シンポジウム
    • Place of Presentation
      東京都江東区青海 産業技術総合研究所 臨海副都心センター
    • Year and Date
      2015-07-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] Cell surface engineering with ssDNA-PEG-lipid for analysing intercellular interactions between different cells2015

    • Author(s)
      Yuji Teramura
    • Organizer
      The 5th Asian Biomaterials Congress
    • Place of Presentation
      台北、台湾
    • Year and Date
      2015-05-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DNA結合PEG脂質を利用した異なる細胞同士の相互作用解析2014

    • Author(s)
      寺村裕治、高井まどか
    • Organizer
      第36回日本バイオマテリアル学会
    • Place of Presentation
      東京都江戸川区船堀 タワーホール船堀
    • Year and Date
      2014-11-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] Cell surface engineering with biomaterials for islet transplantation2014

    • Author(s)
      Yuji Teramura
    • Organizer
      1st Immune Responses to Biosurfaces: Mechanisms and Therapeutic Interventions
    • Place of Presentation
      Chania, Greece
    • Year and Date
      2014-09-27
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] DNA 結合PEG脂質を利用した異種細胞同士の相互作用解析2014

    • Author(s)
      寺村裕治、高井まどか
    • Organizer
      第43 回医用高分子シンポジウム
    • Place of Presentation
      東京都江東区青海 産業技術総合研究所 臨海副都心センター
    • Year and Date
      2014-07-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 高分子による免疫反応の制御のための細胞表面修飾と糖尿病治療への応用2014

    • Author(s)
      寺村裕治
    • Organizer
      第60回高分子研究会(神戸)
    • Place of Presentation
      兵庫県神戸市中央区 兵庫県民会館
    • Year and Date
      2014-07-24
    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] 培養基材への細胞の固定を促進する化合物2015

    • Inventor(s)
      寺村裕治、高井まどか
    • Industrial Property Rights Holder
      寺村裕治、高井まどか
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-205254
    • Filing Date
      2015-10-19
    • Application Year
      2015
    • Related Report
      2015 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-28  

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