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

• Project Area: Hyper 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 Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: The 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: ¥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。

Research Products

• [Int'l Joint Research] ウプサラ大学/リンネア大学(スウェーデン)
• [Int'l Joint Research] オスロ大学/トロムソ大学(ノルウェー)
• [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)
• [Int'l Joint Research] オスロ大学(ノルウェー)
• [Int'l Joint Research] カールスルーエ工科大学(ドイツ)
• [Journal Article] Stable surface coating of silicone elastomer with phosphorylcholine and organosilane copolymer with cross-linking for repelling proteins (2015)
  • Author(s): Koji Nagahashi, Yuji Teramura, Madoka Takai
  • Journal Title: Colloid Surface B Volume: 94 Pages: 384-391
  • DOI: 10.1016/j.colsurfb.2015.07.040
  • Peer Reviewed
• [Journal Article] Cell surface modification with ssDNA-PEG-lipid for analysing intercellular interactions between different cells (2015)
  • Author(s): Yuji Teramura
  • Journal Title: Biomaterials Volume: 48 Pages: 194-205
  • DOI: 10.1016/j.biomaterials.2015.01.032
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma (2015)
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Cell surface engineering for regulation of immune reactions in cell transplantation (2015)
  • 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
  • ISBN: 9783319186023, 9783319186030
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Thromboinflammation in Therapeutic Medicine (2015)
  • 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
  • ISBN: 9783319186023, 9783319186030
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Transplantation of Co-aggregates of Sertoli Cells and Islet Cells into Liver Without Immunosuppression. (2014)
  • Author(s): Naohiro Takemoto, Xibao Liu, Kento Takii, Yuji Teramura, and Hiroo Iwata
  • Journal Title: Transplantation Volume: 97 Issue: 3 Pages: 287-293
  • DOI: 10.1097/01.tp.0000438198.76531.03
  • Peer Reviewed / Open Access
• [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 Issue: 1 Pages: e85040-e85040
  • DOI: 10.1371/journal.pone.0085040
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mediation of a non-proteolytic activation of complement component C3 by phospholipid vesicles (2014)
  • 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 Issue: 11 Pages: 3688-3696
  • DOI: 10.1016/j.biomaterials.2013.12.085
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Lectin-tagged Fluorescent Polymeric Nanoparticles for Targeting of Sialic Acid on the Living Cells (2014)
  • Author(s): Jaebum Cho, Keiichiro Kushiro, Yuji Teramura, Madoka Takai
  • Journal Title: Biomacromolecules Volume: 15 Issue: 6 Pages: 2012-2018
  • DOI: 10.1021/bm500159r
  • 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 Issue: 9 Pages: 2430-2442
  • DOI: 10.1002/stem.1729
  • 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 hepatocyte (2015)
  • 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
  • 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
• [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
• [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
• [Presentation] Cell surface engineering with ssDNA-PEG-lipid for analysing intercellular interactions between different cells (2015)
  • Author(s): Yuji Teramura
  • Organizer: The 5th Asian Biomaterials Congress
  • Place of Presentation: 台北、台湾
  • Year and Date: 2015-05-06
  • 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
• [Presentation] Cell surface engineering with biomaterials for islet transplantation (2014)
  • 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
  • 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
• [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
• [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