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Development of progenitors of bioogical pacemaker from human iPS cells

Research Project

Project/Area Number 17K09580
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionTottori University

Principal Investigator

Hisatome Ichiro  鳥取大学, 医学(系)研究科(研究院), 教授 (60211504)

Co-Investigator(Kenkyū-buntansha) 白吉 安昭  鳥取大学, 医学(系)研究科(研究院), 准教授 (90249946)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
KeywordsiPS cell / biological pacemaker / progenitor / isl1 / HCN4 / pacemaker cell / iPS / human / ペースメーカ幹細胞 / iPS細胞 / 刺激伝導系細胞 / ヒトiPS細胞 / ペースメーカ / 幹細胞
Outline of Final Research Achievements

To compensate the disadvantage of artificial pacemaker (PM), we developed the biological PM cell derived from human iPS cells. Because of the limited ability of their proliferation, we attempted to develop the progenitor of human biological PM. The population of HCN4-GFP positive cells within 14days after differentiation involved the progenitor of PM cells, showing the proliferative activity, where mRNA of isl1 has been enriched. Eventually, we developed the HCN4-GFP/Isl-mCherry double positive cells as the progenitor of PM cells. After characterization of HCN4-GFP/Isl-mCherry double positive cells, we can provide the human biological PM cells derived from their progenitors.

Academic Significance and Societal Importance of the Research Achievements

本研究は機械式ペースメーカに代わる生物学的ペースメーカを十分に供給できる前駆細胞を樹立することを目的として行われ、HCN4-GFP/Isl-mCherry を前駆細胞として樹立できた。本細胞は増殖能力を示し、かつペースメーカ細胞を含む多分化能を有する前駆細胞である。本細胞により、国産生物学的ペースメーカを開発でき、海外特許の機械式ペースメーカに依存しているわが国の医療経済に及ぼすインパクトは計り知れない。

Report

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

    (11 results)

All 2020 2019 2018 2017

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

  • [Journal Article] Multiple Dynamical Mechanisms of Phase-2 Early Afterdepolarizations in a Human Ventricular Myocyte Model: Involvement of Spontaneous SR Ca (2+) Release.2020

    • Author(s)
      Kurata Y, Tsumoto K, Hayashi K, Hisatome I, Kuda Y, Tanida M.
    • Journal Title

      Front Physiol.

      Volume: 10 Pages: 1545-1545

    • DOI

      10.3389/fphys.2019.01545

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibitory effects of class I antiarrhythmic agents on Na+ and Ca2+ currents of human iPS cell-derived cardiomyocytes.2019

    • Author(s)
      Yonemizu S, Masuda K, Kurata Y, Notsu T, Higashi Y, Fukumura K, Li P, Ninomiya H, Miake J, Tsuneto M, Shirayoshi Y, Hisatome I.
    • Journal Title

      Regen Ther.

      Volume: 10 Pages: 104-111

    • DOI

      10.1016/j.reth.2018.12.002

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pretreatment with an angiotensin II receptor blocker abolished ameliorating actions of adipose-derived stem cell sheets on cardiac dysfunction and remodeling after myocardial infarction2018

    • Author(s)
      Yamamoto Kenshiro、Kurata Yasutaka、Inoue Yumiko、Adachi Maya、Tsuneto Motokazu、Miake Junichiro、Ogino Kazuhide、Ninomiya Haruaki、Yoshida Akio、Shirayoshi Yasuaki、Suyama Yoshiko、Yagi Shunjiro、Nishimura Motonobu、Yamamoto Kazuhiro、Hisatome Ichiro
    • Journal Title

      Regenerative Therapy

      Volume: 9 Pages: 79-88

    • DOI

      10.1016/j.reth.2018.08.005

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Isolation and characterization of ventricular-like cells derived from NKX2-5 eGFP/w and MLC2v mCherry/w double knock-in human pluripotent stem cells2018

    • Author(s)
      Yamauchi Kaori、Li Junjun、Morikawa Kumi、Liu Li、Shirayoshi Yasuaki、Nakatsuji Norio、Elliott David A.、Hisatome Ichiro、Suemori Hirofumi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 495 Issue: 1 Pages: 1278-1284

    • DOI

      10.1016/j.bbrc.2017.11.133

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cited4 is related to cardiogenic induction and maintenance of proliferation capacity of embryonic stem cell-derived cardiomyocytes during in vitro cardiogenesis2017

    • Author(s)
      Miake Junichiro、Notsu Tomomi、Higaki Katsumi、Hidaka Kyoko、Morisaki Takayuki、Yamamoto Kazuhiro、Hisatome Ichiro
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 8 Pages: e0183225-e0183225

    • DOI

      10.1371/journal.pone.0183225

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ヒトiPS細胞由来心筋(iCell CMs)の電気生理学的特性とClass 1群抗不整脈薬によるNa+ならびにCa2+ channel阻害効果2018

    • Author(s)
      増田啓一郎、米水彩香、東祐平、福村健太、三明淳一郎、小倉一能、白吉安昭、山本一博、久留一郎
    • Organizer
      第65回日本不整脈心電学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 心臓発生メカニズムの解明を目的とする新規hiPS細胞株の樹立と解析2018

    • Author(s)
      東祐平、福村健太、増田啓一郎、米水彩香、宮城香乃望、足立隆、久留一郎、經遠智一、白吉安昭
    • Organizer
      第41回 日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] ヒトiPS細胞由来心筋(iCell CMs)の電気生理学的特性とClass 1群抗不整脈薬によるNa+ならびにCa2+ channel阻害効果2018

    • Author(s)
      米水彩香、増田啓一郎、東祐平、福村健太、三明淳一郎、小倉一能、白吉安昭、山本一博、久留一郎
    • Organizer
      第17回日本再生医療学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Cited4 is related to cardiogenic induction and maintenance of proliferation capacity of embryonic stem cell-derived cardiomyocytes during in vitro cardiogenesis.2018

    • Author(s)
      Miake J, Notsu T, Yamamoto K, Hisatome I.
    • Organizer
      第108回日本循環器学会集会
    • Related Report
      2017 Research-status Report
  • [Presentation] ヒトiPS細胞に由来する心筋前駆細胞の選別採取とその解析2017

    • Author(s)
      東祐平、福村健太、増田啓一郎、米水彩香、久留一郎、白吉安昭
    • Organizer
      第40回 日本分子生物学会年会
    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 新規刺激伝導系細胞様細胞2018

    • Inventor(s)
      白吉安昭、森川久未、久留一郎
    • Industrial Property Rights Holder
      白吉安昭、森川久未、久留一郎
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-062705
    • Filing Date
      2018
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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