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Addition of human iPS-derived neural progenitors and endothelial cells influences the contractile function of cardiac spheroids.

Research Project

Project/Area Number 17K10732
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular surgery
Research InstitutionSaga University

Principal Investigator

Furukawa Kojiro  佐賀大学, 医学部, 客員研究員 (90264176)

Co-Investigator(Kenkyū-buntansha) 木塚 貴浩  佐賀大学, 医学部, 医員 (20796487)
荒井 健一  佐賀大学, 医学部, 特任助教 (40752960)
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)
迎 洋輔  佐賀大学, 医学部, 助教 (90746570)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsヒトiPS由来スフェロイド / 神経前駆細胞 / 内皮細胞 / 組織工学 / 再生医療 / ヒトiPS細胞由来 / 心筋細胞 / ヒトiPS由来心筋凝集体 / ヒトiPS細胞由来心筋細胞 / ヒトiPS細胞由来神経前駆細胞 / ヒトiPS細胞由来血管内皮細胞 / スフェロイド / 心筋再生
Outline of Final Research Achievements

Neural progenitor cells favored the beating of mixed myocardial spheroids, and histological evaluation confirmed the expression of Nestin and β3tubulin positive cells in the spheroids. In addition, by using a synthetic compound that promotes angiogenesis, stimulates the production and secretion of vascular endothelial growth factor (VEGF), and has a neuroprotective effect in the maturation process of myocardial spheroids mixed with iPS cell-derived vascular endothelial cells, the mixing with the increase in cAMP amount is achieved. It was confirmed that the contraction rate of myocardial spheroids was increased. In this study, we succeeded in producing iPS cell-derived mixed myocardial spheroids that have vascular and neural networks, beating only by cells.

Academic Significance and Societal Importance of the Research Achievements

近年、心筋障害後の神経前駆細胞による新生血管誘導や心筋のRemodelingは注目されており、これまでも動物実験レベルやヒトの移植心臓では各種報告がある。本研究において接着系細胞が元来もつ細胞凝集現象を利用して、細胞のみで拍動し血管網、神経網を有するiPS細胞由来混合型心筋スフェロイドの作製、及びその高機能化に成功した。本基盤技術に組織工学技術を応用することで、免疫応答や感染症が極めて少ない自己細胞のみでできた構造体作製が可能である。ゆえに本成果は近未来の幹細胞を利用した再生医療の臨床応用に向けた一助となり得ると考える。

Report

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

    (14 results)

All 2019 2018 2017

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Book (2 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [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] 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] 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 Research-status 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)
      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 Research-status Report
  • [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] 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] 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] 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] 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 Research-status Report
    • Int'l Joint Research / Invited
  • [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 Research-status Report
    • Invited
  • [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
  • [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: 2017-04-28   Modified: 2021-02-19  

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