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Development of cardiovascular tissue using bio 3D printer, stem cell technology, and elucidation of cellular dynamics in tissue

Research Project

Project/Area Number 16H02674
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Cardiovascular surgery
Research InstitutionSaga University

Principal Investigator

Morita Shigeki  佐賀大学, 医学部, 客員研究員 (70243938)

Co-Investigator(Kenkyū-buntansha) 中山 功一  佐賀大学, 医学部, 教授 (50420609)
伊藤 学  佐賀大学, 医学部, 助教 (50555084)
野出 孝一  佐賀大学, 医学部, 教授 (80359950)
古川 浩二郎  佐賀大学, 医学部, 客員研究員 (90264176)
五條 理志  京都府立医科大学, 医学(系)研究科(研究院), 教授 (90316745)
荒井 健一  佐賀大学, 医学部, 特任助教 (40752960)
戸田 修二  佐賀大学, 医学部, 教授 (80188755)
西田 誉浩  佐賀大学, 医学部, 教授 (50284500)
迎 洋輔  佐賀大学, 医学部, 助教 (90746570)
Project Period (FY) 2016-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥45,240,000 (Direct Cost: ¥34,800,000、Indirect Cost: ¥10,440,000)
Fiscal Year 2020: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2019: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2018: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2017: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2016: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
Keywords組織工学 / 幹細胞技術 / 細胞内動態 / 心血管組織 / バイオ3Dプリンタ / 組織内細胞動態 / 再生医療 / iPS細胞 / バイオ3Dプリンタ / 心臓血管外科 / 心筋再生 / 血管再生 / 人工臓器
Outline of Final Research Achievements

We have developed a bio 3D printer that constructs a three-dimensional cell structure of any shape in a Scaffold free state. We have Succeeded in creating a large, beating three-dimensional (3D) tubular cardiomyocyte without extrinsic Scaffold using human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) . By maturing a tubular structure constructed with a bio 3D printer in a bioreactor, we succeeded in producing a small-diameter artificial blood vessel having a mechanical strength (burst pressure test) of 10 to 20 times or more that of human normal blood pressure. Furthermore, we succeeded in a long-term transplantation experiment into immunodeficient mini pigs to using a artificial blood vessel mainly composed of human-derived fibroblasts.

Academic Significance and Societal Importance of the Research Achievements

細胞を用いて形態学的特徴、力学的作用を有する移植可能な立体的組織を構築するには、一般的には生体融解性ポリマーなどの細胞のscaffold(足場材料)が必要となる。本研究ではscaffoldを使用することなく、大型化した拍動する3次元(3D)管状心筋構造体の作製に成功し、血管構造体においては大動物への長期移植実験に成功した。末期重症心不全や従来のグラフトが移植不能な末期血管不全などに応用でき多くの人類のhealth careに貢献できる可能性が見い出された。機能的な3次元的組織構築に成功した技術は新規性も高く、自己細胞由来臓器作成医療ビジネスモデル成功の可能性がある。

。

Report

(6 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (29 results)

All 2020 2019 2018 2017 2016

All Journal Article (13 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 9 results,  Open Access: 8 results,  Acknowledgement Compliant: 1 results) Presentation (11 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results) Book (4 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Drug response analysis for scaffold-free cardiac constructs fabricated using bio-3D printer2020

    • Author(s)
      Arai Kenichi、Murata Daiki、Takao Shoko、Nakamura Anna、Itoh Manabu、Kitsuka Takahiro、Nakayama Koichi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 8972-8972

    • DOI

      10.1038/s41598-020-65681-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 人工材料を用いない自家細胞製人工血管の可能性と将来展望2020

    • Author(s)
      伊藤 学
    • Journal Title

      臨牀透析

      Volume: 36-5 Pages: 505-506

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Correction: Cryopreservation method for spheroids and fabrication of scaffold-free tubular constructs2020

    • Author(s)
      Arai Kenichi、Murata Daiki、Takao Shoko、Verissiomo Ana Raquel、Nakayama Koichi
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 11 Pages: e0243249-e0243249

    • DOI

      10.1371/journal.pone.0243249

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Scaffold‐Free Bio‐3D Printing Using Spheroids as “Bio‐Inks” for Tissue (Re‐)Construction and Drug Response Tests2020

    • Author(s)
      Murata Daiki、Arai Kenichi、Nakayama Koichi
    • Journal Title

      Advanced Healthcare Materials

      Volume: 9 Issue: 15 Pages: 1901831-1901831

    • DOI

      10.1002/adhm.201901831

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 新たな免疫不全ブタモデルを用いたヒト細胞製人工血管の安全性・有効性検証2020

    • Author(s)
      伊藤 学, 松林久美香, 中山功一, 小林英司
    • Journal Title

      Organ Biology

      Volume: 27-2 Pages: 141-148

    • NAID

      130007888683

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 自己細胞製人工血管の臨床応用2020

    • Author(s)
      伊藤 学, 松林久美香, 中山功一
    • Journal Title

      腎臓内科

      Volume: 12-3 Pages: 354-361

    • NAID

      40022357541

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Development of an immunodeficient pig model allowing long-term accommodation of artificial human vascular tubes2019

    • Author(s)
      Itoh Manabu、Mukae Yosuke、Kitsuka Takahiro、Arai Kenichi、Nakamura Anna、Uchihashi Kazuyoshi、Toda Shuji、Matsubayashi Kumika、Oyama Jun-ichi、Node Koichi、Kami Daisuke、Gojo Satoshi、Morita Shigeki、Nishida Takahiro、Nakayama Koichi、Kobayashi Eiji
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 2244-2244

    • DOI

      10.1038/s41467-019-10107-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 2-Cl-C.OXT-A stimulates contraction through the suppression of phosphodiesterase activity in human induced pluripotent stem cell-derived cardiac organoids.2019

    • Author(s)
      Kitsuka T, Itoh M, Amamoto S, Arai KI, Oyama J, Node K, Toda S, Morita S, Nishida T, Nakayama K.
    • Journal Title

      PLoS One

      Volume: 14 Issue: 7 Pages: 1-15

    • DOI

      10.1371/journal.pone.0213114

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The addition of human iPS cell-derived neural progenitors changes the contraction of human iPS cell-derived cardiac spheroids.2018

    • Author(s)
      Yosuke Mukae、Ryo Noguchi et al
    • Journal Title

      Tissue and Cell

      Volume: Available online 5 May 2018 Pages: 61-67

    • DOI

      10.1016/j.tice.2018.05.002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fabrication of scaffold-free tubular cardiac constructs using a Bio-3D printer.2018

    • Author(s)
      Arai K, Murata D, Verissimo AR, Mukae Y, Itoh M, Nakamura A, Morita S, Nakayama K
    • Journal Title

      PLoS One

      Volume: 13 Issue: 12 Pages: e0209162-e0209162

    • DOI

      10.1371/journal.pone.0209162

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] スキャフォールドフリーバイオ3Dプリンタを用いた小口径細胞製人工血管の開発2017

    • Author(s)
      伊藤学、五條理志、野出孝一、小林英司、森田茂樹、中山功一
    • Journal Title

      医工学治療

      Volume: 29(3) Pages: 167-172

    • Related Report
      2017 Annual Research Report
  • [Journal Article] バイオ3Dプリンティング技術を利用したscaffold free小口径細胞人工血管の開発2016

    • Author(s)
      伊藤 学, 中山功一, 五條理志, 野出孝一, 森田茂樹
    • Journal Title

      血管医学

      Volume: 17(1) Pages: 63-68

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of a Three-Dimensional Prevascularized Scaffold-Free Contractile Cardiac Patch for Treating Heart Disease.2016

    • Author(s)
      Noguchi R, Nakayama K, Itoh M, Kamohara K, Furukawa K, Oyama J, Node K, Morita S.
    • Journal Title

      J Heart Lung Transplant.

      Volume: 35(1) Pages: 137-45

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Translational research of Kenzan method Bio-3D Printer for vascular surgery.2019

    • Author(s)
      Itoh Manabu
    • Organizer
      Thailand-Japan International Symposium for Regenearative Medicine.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 新たな免疫不全ブタモデルを用いたヒト細胞製人工血管の安全性・有効性検証2019

    • Author(s)
      伊藤 学, 中山功一, 小林英司
    • 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
  • [Presentation] 心臓血管再生医療研究と臨床応用に向けて2019

    • Author(s)
      伊藤 学
    • Organizer
      第27回佐賀心不全研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] バイパス治療の役割と人工血管再生医療への取り組み2019

    • Author(s)
      伊藤 学
    • Organizer
      第19回 日本病院総合診療医学
    • Related Report
      2019 Annual Research Report
  • [Presentation] 組織工学を用いた小口径細胞製人工血管の現状と展望2019

    • Author(s)
      伊藤 学
    • Organizer
      第28回 腎疾患治療連携研究会組織工学を用いた小口径細胞製人工血管の現状と展望
    • Related Report
      2019 Annual Research Report
  • [Presentation] 2-Cl-C.OXT-A Stimulates Contraction through Suppression of PDE Activity in HiPSC-Derived Cardiac Organoids2018

    • Author(s)
      Kitsuka T, Itoh M, Amamoto S, Arai K, Oyama J, Node K, Nakayama K, Morita S, Nishida T.
    • Organizer
      AHA Scientific Sessions 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Translational research of scaffold free tubular tissue modeled with Kenzan method Bio-3D Printer for cardiovascular surgery.2018

    • Author(s)
      Manabu Itoh
    • Organizer
      5th TERMIS World Congress 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] バイオ 3D プリンタを用いたチューブ型心筋構造体の作製2017

    • Author(s)
      荒井健一 、小島敦子 、迎 洋輔 、伊藤学 、森田茂樹 、中山功一
    • Organizer
      日本再生医療学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] バイオ3Dプリンティング技術を用いた小口径細胞製人工血管の臨床開発2017

    • Author(s)
      伊藤学
    • Organizer
      第5回先進医工学ブタ研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 心臓血管外科領域における臓器再生への試み2017

    • Author(s)
      伊藤学
    • Organizer
      第11回九州医療センター地域医療研修会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Addition of human iPS-derived neural progenitors influences the contractile function of cardiac spheroids.2016

    • Author(s)
      Mukae Y, Itoh M, Furukawa K, Kitsuka T, Arai K, Oyama J, Nakayama K, Node K, Morita S.
    • Organizer
      Biofabrication
    • Place of Presentation
      North carolina
    • Year and Date
      2016-10-29
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Book] 【再生医療up to date】【多次元構造臓器の再生】スキャフォールドフリー小口径細胞製人工血管 臨床 応用に向けて2019

    • Author(s)
      伊藤 学, 中山功一
    • Total Pages
      5
    • Publisher
      腎と透析
    • Related Report
      2019 Annual Research Report
  • [Book] バイオ3Dプリンティング技術の人工血管分野への医療応用2019

    • Author(s)
      伊藤 学, 野出孝一, 松林久美香, 中山功一
    • Total Pages
      5
    • Publisher
      日本アフェレシス学会雑誌
    • Related Report
      2019 Annual Research Report
  • [Book] スキャフォールドフリー小口径細胞製人工血管―臨床2019

    • Author(s)
      伊藤 学,中山功一
    • Publisher
      腎と透析
    • Related Report
      2018 Annual Research Report
  • [Book] バイオ3Dプリンタを用いた次世代型透析用人工血管の開発2018

    • Author(s)
      伊藤 学
    • Publisher
      日本透析医会雑誌
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 血管拡張器具2019

    • Inventor(s)
      伊籐 学
    • Industrial Property Rights Holder
      伊籐 学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
    • Overseas

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Published: 2016-04-21   Modified: 2022-01-27  

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