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Targeting of stem cells for stroke treatment using PEG-lipid derivatives

Research Project

Project/Area Number 17K20085
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Biomedical engineering and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Teramura Yuji  東京大学, 大学院工学系研究科(工学部), 准教授 (10365421)

Co-Investigator(Kenkyū-buntansha) 児玉 智信  東京慈恵会医科大学, 医学部, 助教 (70449932)
Project Period (FY) 2017-06-30 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Keywords細胞表面修飾 / 脳梗塞 / MSC / PEG脂質 / Eセレクチン / 間葉系幹細胞(MSC) / E-セレクチン / 生体材料 / 移植・再生医療 / 脳・神経
Outline of Final Research Achievements

Promising cell therapies using mesenchymal stem cells (MSCs) is proposed for stroke patients. Therefore, we aimed to efficiently accumulate human MSC (hMSC) to damaged brain area to improve the therapeutic effect using poly(ethylene glycol) (PEG)-conjugated phospholipid (PEG-lipid) carrying an oligopeptide as a ligand, specific for E-selectin which is up-regulated on activated endothelial cells under hypoxia like stroke. Here we synthesized E-selectin-binding oligopeptide (ES-bp) conjugated with PEG spacer. We found that ES-bp can be immobilized onto the hMSC surface through PEG-lipid without influence on cell growth and differentiation into adipocytes and osteocytes, respectively. In addition, the modified hMSC can specifically attach onto E-selectin-immobilized surface as a model surface of activated endothelium, indicating the sufficient number of immobilized ES-bp onto hMSC. Thus, this technique is one of the candidates for hMSC accumulation to cerebral infarction area.

Academic Significance and Societal Importance of the Research Achievements

高齢化の進行に伴い、脳梗塞や脳出血に代表される脳血管障害は、日本人の死亡原因の中でも多くを占めている高頻度な疾患である上、後遺症によって介護が必要となる多くの後遺症に苦しむ脳梗塞患者に対して、自己骨髄由来の幹細胞(間葉系幹細胞(MSC))を用いて、細胞移植により機能回復を目指す画期的治療を効果的に推進できることが可能になる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (27 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (13 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 11 results,  Open Access: 4 results) Presentation (12 results) (of which Int'l Joint Research: 5 results,  Invited: 6 results)

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

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] ウプサラ大学/リンネア大学/スウェーデン農業科学大学(スウェーデン)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Quantitative evaluation of the impact of artificial cell adhesion via DNA hybridization on E-cadherin-mediated cell adhesion2020

    • Author(s)
      Togo Shodai、Sato Ken、Kawamura Ryuzo、Kobayashi Naritaka、Noiri Makoto、Nakabayashi Seiichiro、Teramura Yuji、Yoshikawa Hiroshi Y.
    • Journal Title

      APL Bioengineering

      Volume: 4 Issue: 1 Pages: 016103-016103

    • DOI

      10.1063/1.5123749

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Poly(2-aminoethyl methacrylate)-based polyampholyte brush surface with carboxylic groups to improve blood compatibility2020

    • Author(s)
      Tomoyuki Azuma, Taishi Matsushita, Vivek Anand Manivel, Kristina N Ekdahl, Bo Nilsson, Yuji Teramura and Madoka Takai
    • Journal Title

      J Biomater Sci Polym Ed

      Volume: 31 Issue: 5 Pages: 679-693

    • DOI

      10.1080/09205063.2019.1710900

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Combination of two antithrombogenic methodologies for preventing thrombus formation on a poly(ether ether ketone) substrate2020

    • Author(s)
      Kazuhiko Ishihara, Satoru Yanokuchi, Yuji Teramura, Kyoko Fukazawa
    • Journal Title

      Colloid Surface B

      Volume: - Pages: 111021-111021

    • DOI

      10.1016/j.colsurfb.2020.111021

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 細胞表面の工学的改質がもたらすバイオメディカル分野における可能性2020

    • Author(s)
      寺村裕治、石原一彦
    • Journal Title

      バイオマテリアル

      Volume: 38 Pages: 132-134

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Optimization of Islet Microencapsulation with Thin Polymer Membranes for Long-Term Stability2019

    • Author(s)
      Shota Toda, Kenta Asawa, Artin Fattah, Naoko Nakamura, Kristina N Ekdah, Bo Nilsson, Yuji Teramura
    • Journal Title

      Micromachines

      Volume: 10 Issue: 11 Pages: 755-755

    • DOI

      10.3390/mi10110755

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Modification of human MSC surface with oligopeptide-PEG-lipids for selective binding to activated endothelium2019

    • Author(s)
      Makoto Noiri, Kenta Asawa, Naoya Okada1, Tomonobu Kodama, Yuichi Murayama, Yuuki Inoue, Kazuhiko Ishihara, Kristina N Ekdahl, Bo Nilsson, and Yuji Teramura
    • Journal Title

      J Biomed Mater Res Part A

      Volume: - Issue: 8 Pages: 1779-1792

    • DOI

      10.1002/jbm.a.36697

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Validation of an MPC polymer coating to reduce surface-induced cascade system activation in whole blood in in vitro and in vivo models2019

    • Author(s)
      Sana Asif, Kenta Asawa, Yuuki Inoue, Kazuhiko Ishihara, Bjorn Lindell, Robin Holmgren, Bo Nilsson, Anneli Ryden, Marianne Jensen-Waern, Yuji Teramura, Kristina N Ekdahl
    • Journal Title

      Macromolecular Bioscience

      Volume: - Issue: 5 Pages: 1800485-1800485

    • DOI

      10.1002/mabi.201800485

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Influence of cell adhesive molecules attached onto PEG-lipid-modified fluid surfaces on cell adhesion2018

    • Author(s)
      Makoto Noiri, Keiichiro Kushiro, Shodai Togo, Ken Sato, Hiroshi Y. Yoshikawa, Madoka Takai and Yuji Teramura
    • Journal Title

      Colloid Surface B

      Volume: 175 Pages: 375-383

    • DOI

      10.1016/j.colsurfb.2018.12.015

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rapid and highly efficient capture and release of cancer cells using polymeric microfibers immobilized with enzyme-cleavable peptides2018

    • Author(s)
      Akifumi Yoshihara, Ryota Sekine, Takayuki Ueki, Yasuhito Kondo, Yoshiyuki, Sunaga, Tadashi Nakaji-Hirabayashi, Yuji Teramura and Madoka Takai
    • Journal Title

      Acta Biomaterialia

      Volume: 67 Pages: 32-41

    • DOI

      10.1016/j.actbio.2017.11.055

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Design and Application of Cell Glue2018

    • Author(s)
      寺村裕治
    • Journal Title

      KOBUNSHI RONBUNSHU

      Volume: 75 Issue: 2 Pages: 103-115

    • DOI

      10.1295/koron.2017-0052

    • NAID

      130006528537

    • ISSN
      0386-2186, 1881-5685
    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quartz Crystal Microbalance2018

    • Author(s)
      Yuji Teramura and Madoka Takai
    • Journal Title

      Compendium of Surface and Interface Analysis, Springer, The Surface Science Society of Japan ed

      Volume: - Pages: 509-520

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Quartz Crystal Microbalance2018

    • Author(s)
      Yuji Teramura and Madoka Takai
    • Journal Title

      Compendium of Surface and Interface Analysis

      Volume: なし Pages: 509-520

    • DOI

      10.1007/978-981-10-6156-1_83

    • ISBN
      9789811061554, 9789811061561
    • Related Report
      2017 Research-status Report
  • [Journal Article] Ratiometric fluorescence imaging of cell surface pH by poly(ethylene glycol)-phospholipid conjugated with fluorescein isothiocyanate2017

    • Author(s)
      Ryuichi Ohgaki, Yuji Teramura, Daichi Hayashi, Suguru Okuda, Shushi Nagamori, Madoka Taka and Yoshikatsu Kanai
    • Journal Title

      Sci Res

      Volume: 7 Issue: 1 Pages: 17484-17484

    • DOI

      10.1038/s41598-017-17459-y

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Cell surface modification of stem cells with oligopeptide and the optimization for selective accumulation onto stroke area2019

    • Author(s)
      Yuji Teramura, Makoto Noiri, Naoya Okada, Yuuki Inoue, Ishihara Kazuhiko
    • Organizer
      第68回高分子学会年次大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] PEG脂質による幹細胞表面へのオリゴペプチドの導入と脳梗塞部位への集積を目指した最適化2019

    • Author(s)
      寺村 裕治、野入 信人、岡田 直也、井上 祐貴、石原 一彦
    • Organizer
      第48回医用高分子シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] 細胞表面工学を利用した細胞・臓器移植への展開2019

    • Author(s)
      寺村裕治
    • Organizer
      第46回日本臓器保存生物医学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 幹細胞の脳梗塞部位への集積効率を高めるPEG脂質ペプチド結合体による細胞表面修飾の最適化2019

    • Author(s)
      野入信人, 岡田直也, 井上祐貴, 石原一彦, 寺村裕治
    • Organizer
      第41回日本バイオマテリアル学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 臨床で役に立つ医工学研究を目指して -細胞移植と臓器移植を中心に-2019

    • Author(s)
      寺村裕治
    • Organizer
      第69回医用高分子研究会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Cell surface engineering using amphiphilic polymers for cell manipulation2019

    • Author(s)
      Yuji Teramura
    • Organizer
      Symposium for Crossing Borders in Medical Nanoscience and Biomaterials, Karolinska Institute, Stockholm
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 留置したステントやコイルの血管内皮化度を調べるイメージング材料を目指して2019

    • Author(s)
      寺村裕治
    • Organizer
      東京大学医学部附属病院 先端医療シーズ開発フォーラム2019 「アカデミアによるイノベーションの加速」
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Cell surface engineering for biomedical applications2019

    • Author(s)
      Yuji Teramura
    • Organizer
      The University of Tokyo-iCONM-NANOTEC Joint Research Meeting on Precision Nanomedicine
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Cell surface engineering for biomedical application2018

    • Author(s)
      Yuji Teramura
    • Organizer
      Seminar series in Crossing-Borders, Karolinska Institute, Stockholm
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] PEG 脂質による血管内皮のコーティングとブタ腎移植 における虚血再灌流障害への保護効果2018

    • Author(s)
      寺村裕治, Alireza Biglarnia, Marianne Jensen-Waern, Sana Asif・Kristina Nilsson-Ekdahl・Bo Nilsson
    • Organizer
      第47回医用高分子シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] Protective role of PEG-phospholipid conjugate in reducing ischemic reperfusion injury in kidney transplantation2018

    • Author(s)
      Yuji Teramura, Sana Asif, Kristina N. Ekdahl, Elin Manell, Alireza Biglarnia, Marianne Jensen-Waern, Bo Nilsson
    • Organizer
      Biointerfaces International 2018 Zurich
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] A new cell glue for 3D cell structures: Induced cell adhesion using surface modification with cellpenetrating peptide-PEG-lipid2018

    • Author(s)
      Yuji Teramura, Sana Asif, Kristina N. Ekdahl, Elisabet Gustafson, Bo Nilsson
    • Organizer
      5th TERMIS World Congress-2018 Kyoto
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2017-07-21   Modified: 2023-03-16  

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