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Creation of functional heart tissues with perfusable vasculature using in vivo prevascularization techniques

Research Project

Project/Area Number 19H04453
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 90110:Biomedical engineering-related
Research InstitutionTokyo Women's Medical University

Principal Investigator

Sekine Hidekazu  東京女子医科大学, 医学部, 准教授 (60541737)

Co-Investigator(Kenkyū-buntansha) 本間 順  東京女子医科大学, 医学部, 助教 (50507366)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords組織工学 / 心筋再生 / 血管新生 / 血管床 / 循環補助 / 細胞シート / 心不全 / 再生医療 / 心筋組織 / 生体内チャンバー / バイオリアクター / 立体組織 / 段階的積層化 / 血管網導入 / 心筋カフ / 毛細血管
Outline of Research at the Start

細胞の多層化による立体組織の構築には、酸素や栄養の供給・老廃物の除去が拡散のみでは限界があるため、構築組織内への血管網付与技術の確立が必須となっている。我々はこれまでに小動物(ラット)を用い、外科的処置によりインビボで閉鎖系動静脈回路を再構築した血管床上へ心筋細胞シートを積層し、組織への十分な血管新生を待って繰り返し積層する段階的移植法を開発し、生体内と生体外の両方の環境において毛細血管網をともなった厚い心筋組織の構築に成功している。本研究ではこの技術を大動物(ブタ)へ発展させ臨床応用可能な血管付き高機能ヒト心筋組織を創製する。

Outline of Final Research Achievements

A major challenge in myocardial tissue engineering is that inadequate oxygen and nutrients supply to engineered 3D myocardial tissue limits the thickness of the fabricated tissue to about 100-200μm. Therefore, techniques to control the growth and formation of blood vessels are needed to fabricate thicker and more functional myocardial tissue. To address this issue, we have developed a method of inserting a vascular network by in vivo pre-vascularization, in which capillaries are reconstructed in vivo. By using it to create multiple layers of cell sheets, a cuff-shaped three-dimensional cardiac tissue with a thickness of 1 mm that can assist blood circulation was then realized.

Academic Significance and Societal Importance of the Research Achievements

本研究の技術をさらに発展させることで、重症心不全患者のための細胞から作製する循環補助システムの構築が可能となる。これを臨床応用できた場合には、疾患の根治または大幅改善が期待できる。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (12 results)

All 2022 2021 2020 2019

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Book (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Bioartificial pulsatile cuffs fabricated from human induced pluripotent stem cell-derived cardiomyocytes using a pre-vascularization technique2022

    • Author(s)
      Yuki Endo, Jun Homma, Hidekazu Sekine, Katsuhisa Matsuura, Tatsuya Shimizu, Hiroshi Niinami
    • Journal Title

      npj Regenerative Medicine

      Volume: 7 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41536-022-00218-7

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Perfusable vascular tree like construction in 3D cell-dense tissues using artificial vascular bed2022

    • Author(s)
      Yusuke Tobe, Jun Homma, Katsuhisa Skaguchi, Hidekazu Sekine, Kiyotaka Iwasaki, Tatsuya Shimizu
    • Journal Title

      Microvascular research

      Volume: 141 Pages: 104321-104321

    • DOI

      10.1016/j.mvr.2022.104321

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Capillary Networks for Bio-Artificial Three-Dimensional Tissues Fabricated Using Cell Sheet Based Tissue Engineering2021

    • Author(s)
      Hidekazu Sekine, Teruo Okano
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 1 Pages: 1-12

    • DOI

      10.3390/ijms22010092

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Engineering of functional cardiac tubes by stepwise transplantation of cardiac cell sheets onto intestinal mesentery2020

    • Author(s)
      Noriyasu Masuda, Hidekazu sekine, Hiroshi Niinami, Tatsuya Shimizu
    • Journal Title

      Heart and Vessels

      Volume: - Issue: 6 Pages: 859-867

    • DOI

      10.1007/s00380-019-01550-7

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of a large-scale vascular bed for the in vitro creation of three-dimensional cardiac tissue2019

    • Author(s)
      Akitoshi Inui, Hidekazu Sekine, Kazunori Sano, Izumi Dobashi, Azumi Yoshida, Katsuhisa Matsuura, Eiji Kobayashi, Minoru Ono, Tatsuya Shimizu
    • Journal Title

      Regenerative Therapy

      Volume: 11 Pages: 316-323

    • DOI

      10.1016/j.reth.2019.10.001

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 血液循環補助可能な人工的カフ型ヒト心筋組織の作製2022

    • Author(s)
      遠藤祐輝, 本間順, 関根秀一, 松浦勝久, 清水達也, 新浪博士
    • Organizer
      第21回日本再生医療学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 生体外における灌流可能な血管網の高細胞密度の立体組織への付与技術の開発2022

    • Author(s)
      戸部 友輔: 本間 順:, 坂口 勝久, 関根 秀一, 岩﨑 清隆, 清水 達也
    • Organizer
      第21回日本再生医療学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] In vivo vascularization for tissue and organ fabrication2019

    • Author(s)
      Hidekazu Sekine
    • Organizer
      TERMIS-AP 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] Methods in Molecular Biology2022

    • Author(s)
      Hidekazu Sekine, Teruo Okano
    • Total Pages
      309
    • Publisher
      Springer Nature
    • ISBN
      9781071622605
    • Related Report
      2022 Annual Research Report
  • [Book] Cell Sheets for Cardiac Tissue Engineering2020

    • Author(s)
      Hidekazu Sekine, Jun Homma, Tatsuya Shimizu
    • Total Pages
      19
    • Publisher
      Springer International Publishing
    • ISBN
      9783030442101
    • Related Report
      2020 Annual Research Report
  • [Book] Tissue Engineering and Regeneration. Organ Tissue Engineering2020

    • Author(s)
      Hidekazu Sekine, Jun Homma, Tatsuya Shimizu
    • Publisher
      Springer
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 人工血管床、人工三次元生体組織及び血管網を備えた人工三次元生体組織の作製方法2021

    • Inventor(s)
      戸部友輔、本間順、関根秀一、坂口勝久、清水達也
    • Industrial Property Rights Holder
      戸部友輔、本間順、関根秀一、坂口勝久、清水達也
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-182725
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report

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Published: 2019-04-18   Modified: 2024-01-30  

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