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Induction of vasculogenesis and angiogenesis in three-dimensional tissues by using protein expressions with mRNA delivery

Research Project

Project/Area Number 18H03537
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 90120:Biomaterials-related
Research InstitutionTokyo Women's Medical University

Principal Investigator

Kobayashi Jun  東京女子医科大学, 医学部, 講師 (20385404)

Co-Investigator(Kenkyū-buntansha) 秋山 義勝  東京女子医科大学, 医学部, 講師 (20349640)
増田 信奈子  東京女子医科大学, 医学部, 助教 (30342851)
中山 正道  東京女子医科大学, 医学部, 講師 (00338980)
辰巳 公平  奈良県立医科大学, 医学部, 准教授 (70555432)
山岡 哲二  国立研究開発法人国立循環器病研究センター, 研究所, 部長 (50243126)
長瀬 健一  慶應義塾大学, 薬学部(芝共立), 准教授 (10439838)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2020: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2019: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywords細胞シート / 血管新生 / 脈管形成 / mRNA送達 / 血管内皮前駆細胞 / 血管前駆細胞
Outline of Final Research Achievements

In this study, we developed a novel technique to induce angiogenesis in 3D cell sheet tissue and promote angiogenesis to connect with a host blood vessel. By introducing VEGF-encoding messenger RNA (mRNA) into the 3D cell sheet tissue and allowing it to act like a paracline in the vicinity of vascular endothelial cells, it was suggested to induce angiogenesis inside the 3D cell sheet tissue. It was also found that transplantable liver / cardiomyocyte sheets that rapidly secrete VEGF can be prepared by mRNA delivery. Furthermore, by stacking these, it can be expected to be applied to the construction of a functional three-dimensional tissue having a capillary-like structure of endothelial cells.

Academic Significance and Societal Importance of the Research Achievements

mRNAを利用した脈管形成と同様の内容はこれまでに報告されていない。また、移植可能な3D組織の構築が実現されれば、これまでに不可能であった肝組織の効率的な移植方法につながり、組織再生治療分野における大きなブレークスルーとなると同時に、肝組織再生治療の臨床応用への展開が期待される。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (17 results)

All 2022 2021 2020 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (16 results) (of which Int'l Joint Research: 6 results,  Invited: 1 results)

  • [Journal Article] Preservation of heparin-binding EGF-like growth factor activity on heparin-modified poly(N-isopropylacrylamide)-grafted surfaces2021

    • Author(s)
      KOBAYASHI Jun, ARISAKA Yoshinori, YUI Nobuhiko, YAMATO Masayuki, OKANO Teruo
    • Journal Title

      RSC Advances

      Volume: 11 (59) Issue: 59 Pages: 37225-37232

    • DOI

      10.1039/d1ra07317f

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Ex Vivo Gene Delivery for Fabrication of Hepatocyte Sheet Tissues Secreting Angiogenic Factors2022

    • Author(s)
      KOBAYASHI Jun, LEE Hyukjin, YAMATO Masayuki, OKANO Teruo
    • Organizer
      Society for Biomaterials/Japanese Society for Biomaterials Hawaii Joint Symposium
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヘパリン修飾温度応答性高分子グラフト表面に結合したヘパリン結合EGF様増殖因子の活性維持2022

    • Author(s)
      小林純, 有坂慶紀, 由井伸彦, 大和雅之, 岡野光夫
    • Organizer
      第21回日本再生医療学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] IVT-mRNAを利用した成長因子を分泌する細胞シートの作製の検討2022

    • Author(s)
      秋山義勝, KWON Hyo Kyoung, 原口裕次, 坂口勝久, 大和雅之, LEE Hyukjin , 清水達也
    • Organizer
      第21回日本再生医療学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Gene delivery for creation of hepatocyte sheets secreting angiogenic factors2021

    • Author(s)
      KOBAYASHI Jun, LEE Hyukjin, YAMATO Masayuki, OKANO Teruo
    • Organizer
      ISSCR/JSRM 2021 Tokyo International Symposium
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Messenger RNA delivery for fabrication of hepatocyte tissues secreting angiogenic factors2021

    • Author(s)
      KOBAYASHI Jun, LEE Hyukjin, YAMATO Masayuki, OKANO Teruo
    • Organizer
      The 43rd Annual Meeting of the Japanese Society for Biomaterials and The 8th Asian Biomaterials Congress
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 血管新生因子を分泌する肝細胞シート組織作製のための遺伝子デリバリー2021

    • Author(s)
      小林純, LEE Hyukjin, 大和雅之, 岡野光夫
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 血管内皮細胞網形成のためのVEGF mRNA送達積層化細胞シート組織の作製2020

    • Author(s)
      長瀬健一, 白木 義基, 小林純, Lee:Hyukjin, 大和雅之, 金澤秀子
    • Organizer
      第19回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 肝組織工学のためのバイオマテリアル2020

    • Author(s)
      小林純
    • Organizer
      第36回日本DDS学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Creation of transplantable hepatocyte sheet tissues by using thermoresponsive cell culture surfaces2020

    • Author(s)
      KOBAYASHI Jun, LEE Hyukjin, YAMATO Masayuki, OKANO Teruo
    • Organizer
      11th World Biomaterials Congress
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Temperature-dependent binding of growth factors and cells to a heparin-immobilized thermoresponsive surface2019

    • Author(s)
      Jun Kobayashi, Yoshikatsu Akiyama, Masayuki Yamato, Teruo Okano
    • Organizer
      Society For Biomaterials 2019 Annual Meeting and Exposition
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 肝細胞シート組織の機能維持と生体移植のためのバイオマテリアル2019

    • Author(s)
      小林純, Hyukjin Lee, 大和雅之, 岡野光夫
    • Organizer
      第68回高分子討論会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 三次元細胞シート組織内血管網様構造の構築を目指したVEGF mRNAの送達2019

    • Author(s)
      白木義基, 小林純, Hyukjin Lee, 大和雅之, 長瀬健一, 金澤秀子
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 血管新生因子を分泌する肝細胞シート組織作製のための核酸送達2019

    • Author(s)
      小林純, Hyukjin Lee, 大和雅之, 岡野光夫
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Temperature-dependent affinity binding of heparin-binding growth factors and cells with a heparin-immobilized thermoresponsive surface2018

    • Author(s)
      Jun Kobayashi, Yoshikatsu Akiyama, Masayuki Yamato, Teruo Okano
    • Organizer
      5th TERMIS World Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 肝細胞シート組織からの血管新生因子分泌を誘導するための核酸送達2018

    • Author(s)
      小林純, Hyukjin Lee, 大和雅之, 岡野光夫
    • Organizer
      第40回日本バイオマテリアル学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] IVT-mRNAを利用した目的の成長因子を分泌する細胞シート作製の検討2018

    • Author(s)
      秋山義勝, Hyo Kyoung Kwon, 原口裕次, 大和雅之, Hyukjin Lee, 清水達也
    • Organizer
      第40回日本バイオマテリアル学会大会
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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