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Isolation and characterization of cardiac pacemaking cells derived from human embryonic stem cells

Research Project

Project/Area Number 25893134
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field General physiology
Research InstitutionTottori University

Principal Investigator

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

Project Period (FY) 2013-08-30 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsペースメーカ細胞 / ヒトES細胞 / HCN4 / Ifチャネル / 分化誘導 / 心筋細胞 / 自動能 / 可視化 / ペースメーカ / イオンチャネル / 心臓
Outline of Final Research Achievements

The difficulty of preparation in vivo hampered us to analyze directly human sino-atrial pacemaker cells. Therefore we have established the experimental system for preparation of human pacemaker cells derived from human embryonic stem cells (hESCs). In this system, HCN4 positive cells were specifically visualized with CFP (cyan fluorescent protein). The sorted CFP positive cells from hESCs expressed HCN4 maker gene and displayed If current, which could resulted in the automaticity of those cells. Thus CFP positive cells from differentiating hESCs have the essentially same properties with sino-atrial pacemaker cells, including the gene expression profiles, electrophysiological properties. In addition, we targeted mCherry to the MLC2v locus, a good maker for ventricular cells, in the HCN4CFP-BAC hESCs by using CRIPER/CAS9 system. Currently we purified and analyzed HCN4 positive pacemaker cells and MLC2v positive ventricular cells to characterize the cardiac cells with human origin.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • Research Products

    (20 results)

All 2015 2014 2013 Other

All Journal Article (9 results) (of which Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (6 results) (of which Invited: 1 results) Remarks (5 results)

  • [Journal Article] <b>Adipose stem cell sheets improved cardiac function in the rat myocardial infarction, but did not alter cardiac contractile responses to β-adrenergic stim</b><b>ulation </b>2015

    • Author(s)
      Otsuki Y, Nakamura Y, Harada S, Yamamoto Y, Ogino K, Morikawa K, Ninomiya H, Miyagawa S, Sawa Y, Hisatome I, Nishimura M.
    • Journal Title

      Biomedical Research

      Volume: 36 Issue: 1 Pages: 11-19

    • DOI

      10.2220/biomedres.36.11

    • NAID

      130004903877

    • ISSN
      0388-6107, 1880-313X
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] <b>VEGF secretion by adipose tissue-derived regenerative cells is impaired under hyperglycemic conditions via glucose transporter activation and ROS incr</b><b>ease </b>2014

    • Author(s)
      Matsugami H, Harada Y, Kurata Y, Yamamoto Y, Otsuki Y, Yaura H, Inoue Y, Morikawa K, Yoshida A, Shirayoshi Y, Suyama Y, Nakayama B, Iwaguro H, Yamamoto K, Hisatome I.
    • Journal Title

      Biomedical Research

      Volume: 35 Issue: 6 Pages: 397-405

    • DOI

      10.2220/biomedres.35.397

    • NAID

      130004903869

    • ISSN
      0388-6107, 1880-313X
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Instability of KCNE1-D85N that Causes Long QT Syndrome: Stabilization by Verapamil2014

    • Author(s)
      Sakata S, Kurata Y, Li P, Notsu T, Morikawa K, Miake J, Higaki K, Yamamoto Y, Yoshida A, Shirayoshi Y, Yamamoto K, Horie M, Ninomiya H, Kanzaki S, Hisatome I.
    • Journal Title

      Pacing Clinical Electrophysiology

      Volume: Epub ahead of print Issue: 7 Pages: 1-11

    • DOI

      10.1111/pace.12360

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bepridil Suppresses Apoptosis in HL-1 Cardiac Atrial Myocytes Expressing Mutant E334K cMyBPC.2013

    • Author(s)
      Endo R, Notsu T, Mishima M, Morikawa K, Li P, Ikeda N, Ninomiya H, Shirayoshi Y, Hisatome I.
    • Journal Title

      Yonago Acta Medica

      Volume: 56(4) Pages: 93-95

    • NAID

      120005350605

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hsp90 prevents interaction between CHIP and HERG proteins to facilitate maturation of wild-type and mutant HERG proteins2013

    • Author(s)
      Iwai C, P Li,
    • Journal Title

      Cardiovasc Res

      Volume: 3 Issue: 3 Pages: 520-528

    • DOI

      10.1093/cvr/cvt200

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Simultaneous Treatment with Azelnidipine and Olmesartan Inhibits Apoptosis of Hl-1 Cardiac Myocytes Expressing E334k cMyBPC2013

    • Author(s)
      Bahrudin U, Ikeda N, Utami SB, Maharani N, Morikawa K, Li P
    • Journal Title

      Drug Res (Stuttg).

      Volume: 10 Issue: 10 Pages: 515-520

    • DOI

      10.1055/s-0033-1347188

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 胚性幹細胞からの機能的な甲状腺の作出2013

    • Author(s)
      森川久未, 久留一郎, 吉田明雄
    • Journal Title

      日本甲状腺学会雑誌

      Volume: 4(1) Pages: 68-69

    • Related Report
      2013 Annual Research Report
  • [Journal Article] 脂肪由来幹細胞による再生医療2013

    • Author(s)
      森川久未, 久留一郎
    • Journal Title

      鳥取県西部医師会報

      Volume: 170 Pages: 23-25

    • Related Report
      2013 Annual Research Report
  • [Journal Article] AMP deaminase 3 plays a critical role in remote reperfusion lung injury2013

    • Author(s)
      Li P, Ogino K, Morikawa K, Shirayoshi Y, Hisatome I, et al.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 431(2) Issue: 1 Pages: 131-6

    • DOI

      10.1016/j.bbrc.2013.03.056

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] ISOLATION AND CHARACTERIZATION OF HCN4 POSITIVE CELLS DERIVED FROM HUMAN EMBRYONIC STEM CELLS2015

    • Author(s)
      Morikawa K, Nozaki D, Shirayoshi Y, Hisatome I.
    • Organizer
      International Society for Stem Cell Research 13th Annual Meeting
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      2015-06-24 – 2015-06-27
    • Related Report
      2014 Annual Research Report
  • [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
    • Year and Date
      2015-05-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] HCN4 Positive Cells Derived from Pluripotent Stem Cells Show Automaticity and Pacemaking Ability2015

    • Author(s)
      Shirayoshi Y, Morikawa K, Miake J, Hisatome I
    • Organizer
      The 79th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      大阪国際会議場, 大阪
    • Year and Date
      2015-04-24 – 2015-04-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 高血糖は糖輸送体を介して脂肪由来間葉系幹細胞の血管新生能を障害する2015

    • Author(s)
      松上 紘生, 原田 雄輔, 森川 久未, 山本 康孝, 陶山 淑子, 中山 敏, 吉田 明雄, 白吉 安昭, 齋藤 憲輝, 久留 一郎
    • Organizer
      第14回日本再生医療学会総会
    • Place of Presentation
      パシフィコ横浜, 神奈川
    • Year and Date
      2015-03-19 – 2015-03-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] 乳房再建治療メカニズムの解明に向けた乳房再建モデルマウス作製の試み2015

    • Author(s)
      森川 久未, 八浦 妃佐子, 陶山 淑子, 中山 敏, 久留 一郎
    • Organizer
      第14回日本再生医療学会総会
    • Place of Presentation
      パシフィコ横浜, 神奈川
    • Year and Date
      2015-03-19 – 2015-03-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] Electrical Properties of Human iPS Cells-derived Cardiac Myocytes from the Patient with Long QT Syndrome Harboring a Novel Mutation of KCNQ12014

    • Author(s)
      Sogo T, Ichinose T, Morikawa K, Ikeda N, Shirayoshi Y, Kurata Y, Miake J, Yamamoto K, Yuasa S, Fukuda K, Hisatome I
    • Organizer
      第29回 日本不整脈学会・第31回 日本心電学会 合同学術大会
    • Place of Presentation
      東京プリンスホテル, 東京
    • Year and Date
      2014-07-22 – 2014-07-25
    • Related Report
      2014 Annual Research Report
  • [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
      2014 Annual Research 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/departments/center/next-generation-advanced-medical-promotion-center/

    • Related Report
      2014 Annual Research 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
      2014 Annual Research Report
  • [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
      2013 Annual Research Report
  • [Remarks] 次世代高度医療推進センター|鳥取大学医学部附属病院

    • URL

      http://www2.hosp.med.tottori-u.ac.jp/departments/center/next-generation-advanced-medical-promotion-center/

    • Related Report
      2013 Annual Research Report

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Published: 2013-09-12   Modified: 2019-07-29  

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