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Evaluation of cardiac automaticity using human cardiac pacemaking cells derived from human embryonic stem/ induced pluripotent stem cells

Research Project

Project/Area Number 15K21170
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General physiology
Cardiovascular medicine
Research InstitutionTottori University

Principal Investigator

Morikawa Kumi  鳥取大学, 医学部附属病院, 助教 (90707217)

Co-Investigator(Renkei-kenkyūsha) HISATOME Ichiro  鳥取大学, 医学系研究科, 教授 (60211504)
SHIRAYOSHI Yasuaki  鳥取大学, 医学系研究科, 准教授 (90249946)
Research Collaborator YAZAWA Masayuki  
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsペースメーカ細胞 / ヒトES/iPS細胞 / HCN4 / Ifチャネル / 再生医学 / イオンチャネル / 心臓 / 自動能 / 選別分取
Outline of Final Research Achievements

Cardiac beating function originates from cardiac pacemaker cells localized in sino-atrial node. The pacemaker cells produce the electrical pulse automatically and lead the contraction of whole heart. However, it is very difficult to isolate the pacemaker cells from human heart directly. To solve this problem, we have developed a novel system for isolating pacemaker cells (HCN4 positive) derived from human embryonic stem /induced pluripotent stem (ES/iPS) cells.
In this study, we have established the dual cardiac fluorescent reporter human ES/iPS cells, in which HCN4 ion-channel and MLC2v myosin light chain gene are knocked-in with eGFP and mCherry, respectively. Electrophysiological analysis indicated that sorted eGFP positive cells showed the same phenotypes as in vivo pacemaker cells on automaticity and If currents. In conclusion, our system provides a useful platform to study the molecular mechanisms underlying cardiac automaticity as well as regenerative medicine for bradycardia.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (23 results)

All 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (13 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Remarks (4 results)

  • [Int'l Joint Research] Columbia University(米国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Molecular mechanisms underlying the pilsicainide-induced stabilization of hERG proteins in transfected mammalian cells2017

    • Author(s)
      Onohara, Takeshi; Hisatome, Ichiro; Kurata, Yasutaka; Li, Peili; Notsu, Tomomi; Morikawa, Kumi; Otani, Naoyuki; Yoshida, Akio; Iitsuka, Kazuhiko; Kato, Masaru; Miake, Junichiro; Ninomiya, Haruaki; Higaki, Katsumi; Shirayoshi, Yasuaki; Nishihara, Takashi; Itoh, Toshiyuki; Nakamura, Yoshinobu; Nishimura, Motonobu
    • Journal Title

      J. Arrhythmia,

      Volume: 32 Issue: 3 Pages: 226-233

    • DOI

      10.1016/j.joa.2016.09.003

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Electrophysiological properties of iPS cell-derived cardiomyocytes from a patient with long QT syndrome type 1 harboring the novel mutation M437V of KCNQ12016

    • Author(s)
      Sogo T, Morikawa K, Kurata Y, Li P, Ichinose T, Yuasa S, Nozaki D, Miake J, Ninomiya H, Shimizu W, Fukuda K, Yamamoto K, Shirayoshi Y, Hisatome I.
    • Journal Title

      Regenerative Therapy

      Volume: 4 Pages: 9-17

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 生物学的ペースメーカの展望2016

    • Author(s)
      森川久未, 白吉安昭, 久留一郎.
    • Journal Title

      心電図

      Volume: 34(4) Pages: 264-268

    • NAID

      130005139479

    • Related Report
      2015 Research-status Report
  • [Journal Article] Molecular Mechanisms Underlying Urate-Induced Enhancement of Kv1.5 Channel Expression in HL-1 Atrial Myocytes2015

    • Author(s)
      Maharani N, Ting YK, Cheng J, Hasegawa A, Kurata Y, Li P, Nakayama Y, Ninomiya H, Ikeda N, Morikawa K, Yamamoto K, Makita N, Yamashita T, Shirayoshi Y, Hisatome I.
    • Journal Title

      Circulation Journal

      Volume: 79 Issue: 12 Pages: 2659-2668

    • DOI

      10.1253/circj.CJ-15-0416

    • NAID

      130005110934

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Stabilization of Kv1.5 channel protein by the inotropic agent olprinone.2015

    • Author(s)
      Endo R, Kurata Y, Notsu T, Li P, Morikawa K, Kondo T, Ogura K, Miake J, Yoshida A, Shirayoshi Y, Ninomiya H, Higaki K, Kuwabara M, Yamamoto K, Inagaki Y, Hisatome I.
    • Journal Title

      Eur J Pharmacol.

      Volume: 765 Pages: 488-494

    • DOI

      10.1016/j.ejphar.2015.09.013

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Fluorescent human iPS reporter lines offer useful platforms to study cardiac subtype specification and cell-based therapies of cardiac disease.2017

    • Author(s)
      Yasuaki Shirayoshi, Kenta Fukumura, Kumi Morikawa, Ichiro Hisatome
    • Organizer
      ISSCR (International Society of Stem Cell Research) 2017 Annual Meeting
    • Place of Presentation
      Boston, Boston Convention and Exhibition Center
    • Year and Date
      2017-06-14
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Fluorescent Human iPS/ES Reporter Lines Offer the Opportunity to Track Cardiac Subtype Cells in Cell-based Therapies and Drug Development.2017

    • Author(s)
      Yasuaki Shirayoshi, Kumi Morikawa, Kenta Fukumura, Ichiro Hisatome
    • Organizer
      第81回 日本循環器学会学術集会
    • Place of Presentation
      金沢, 石川県立音楽堂他
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] 虚血性心不全モデルに対する脂肪幹細胞シートと心不全薬の併用効果の検討2017

    • Author(s)
      山本堅士郎、丹野翔伍、足立真彩、森川久未、大月優樹、大谷直由、陶山淑子、八木俊路朗、荻野和秀、三明淳一朗、白吉安昭、山本一博、西村元延、久留一郎
    • Organizer
      第16回 日本再生医療学会総会
    • Place of Presentation
      仙台、仙台国際センター
    • Year and Date
      2017-03-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヒトiPS細胞に由来するHCN4陽性心筋前駆細胞の解析2016

    • Author(s)
      福村健太、横井文香、森川久未、野崎大蔵、久留一郎、白吉安昭
    • Organizer
      第39回 日本分子生物学会年会
    • Place of Presentation
      横浜, パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] 選別純化したヒト多能性幹細胞由来分化誘導心筋に関する電気生理学的特性と薬剤応答性の評価2016

    • Author(s)
      白吉安昭、森川久未、山内香織、横井文香、福村健太、野崎大蔵、末盛博文、久留一郎
    • Organizer
      第43回 日本毒性学会
    • Place of Presentation
      名古屋, ウインクあいち
    • Year and Date
      2016-06-29
    • Related Report
      2016 Annual Research Report
  • [Presentation] Generation of Biological Pacemaker Derived from Human Pluripotent Stem Cells2016

    • Author(s)
      Yasuaki Shirayoshi, Kumi Morikawa, Junichiro Miake, Ichiro Hisatome
    • Organizer
      The80th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Stabilization of Kv1.5 Channel Protein by Olprinone as a Chemical Chaperone2016

    • Author(s)
      Ryo Endo, Yasutaka Kurata, Peili Li, Kumi Morikawa, Takehito Kondo, Kazuyoshi Ogura, Junichiro Miake, Kazuhiro Yamamoto, Yasuaki Shirayoshi, Ichiro Hisatome
    • Organizer
      The80th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
  • [Presentation] Electrophysiological Properties of iPS Cell-Derived Cardiomyocytes from a Patient with LQT1 Harboring the Novel Mutation M437V of KCNQ12016

    • Author(s)
      Yasutaka Kurata, Peili Li, Kumi Morikawa, Junichiro Miake, Kazuhiro Yamamoto, Yasuaki Shirayoshi, Ichiro Hisatome
    • Organizer
      The80th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
  • [Presentation] Stabiliation of Kv1.5 Channel Protein by Olprinone2015

    • Author(s)
      Ryo Endo, Yasutaka Kurata, Peili Li, Kumi Moeikawa, Tatehito Kondo, Kazuyoshi Ogura, Junichiro Miake, Kazuhiro Yamamoto, Yasuaki Shirayoshi, Ichiro Hisatome
    • Organizer
      第32回日本心電学会学術集会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2015-07-28
    • Related Report
      2015 Research-status Report
  • [Presentation] Electrophysiological properties of iPS cell-derived cardiomyocytes from a patient with long QT syndrome type 1 harboring a novel mutation of KCNQ12015

    • Author(s)
      Yasutaka Kurata, Peili Li, Kumi Moeikawa, Junichiro Miake Kazuhiro Yamamoto, Yasuaki Shirayoshi, Ichiro Hisatome
    • Organizer
      第32回日本心電学会学術集会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2015-07-28
    • Related Report
      2015 Research-status Report
  • [Presentation] Isolation and Characterization of HCN4 positive cells derived from human embryonic stem cells2015

    • Author(s)
      Kumi Morikawa, Nozaki Daizou, Yasuaki Shirayoshi, Ichiro Hisatome
    • Organizer
      ISSCR (International Society of Stem Cell Research) 13th Annual Meeting
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      2015-06-24
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 生物学的ペースメーカ細胞による再生医療を目指して2015

    • Author(s)
      森川久未
    • Organizer
      第7回再生医療学フォーラムin山陰
    • Place of Presentation
      米子全日空ホテル(鳥取県米子市)
    • Year and Date
      2015-05-25
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] HCN4 Positive Cells Derived from Pluripotent Stem Cells Show Automaticity and Pacemaking Ability2015

    • Author(s)
      Yasuaki Shirayoshi, Kumi Morikawa, Junichiro Miake, Ichiro Hisatome
    • Organizer
      The79th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2015-04-24
    • Related Report
      2015 Research-status Report
    • Invited
  • [Remarks] 鳥取大学大学院医学系研究科 機能再生医科学専攻 遺伝子再生医療学講座 再生医療学部門

    • URL

      http://www.med.tottori-u.ac.jp/regmed/

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
  • [Remarks] 生物学的心臓ペースメーカー細胞の作成とその応用

    • URL

      http://www.med.tottori-u.ac.jp/introduction/grad/297/430/563/1345.html

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
  • [Remarks] 鳥取大学医学部附属病院 次世代高度医療推進センター

    • URL

      http://www2.hosp.med.tottori-u.ac.jp/jisedai/

    • Related Report
      2015 Research-status Report
  • [Remarks] 鳥取大学医学部附属病院 次世代高度医療推進センター Facebook

    • URL

      https://www.facebook.com/1434214006896403/

    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2022-02-16  

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