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Establishment of human pluripotent stem cell-derived pace-making cells using physiological approach and its application to the regenerative medicine

Research Project

Project/Area Number 23659112
Research Category

Grant-in-Aid for Challenging Exploratory Research

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

Principal Investigator

HISATOME Ichiro  鳥取大学, 大学院・医学系研究科, 教授 (60211504)

Co-Investigator(Kenkyū-buntansha) SHIRAYOSHI Yasuaki  鳥取大学, 医学研究科, 准教授 (90249946)
YAMAMOTO Yasutaka  鳥取大学, 医学研究科, 特任准教授 (20362882)
MIAKE Junichiro  鳥取大学, 医学部, 講師 (40372677)
Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordshuman ES cells / HCN4 / pacemaking cells / ヒトES細胞 / ヒトiPS細胞 / HCN4搭載BACベクター / ヒトES細胞 / ペースメーカ細胞
Research Abstract

We attempted to establish the human ES cells harboringHCN4-GFP BAC vector to isolate human pluripotent stem cell-derived pace-making cells using physiological approach. We construct BAC vector harboring the knocked GFP gene into the promoter region of HCN4 gene and introduced it into human ES cells (KhES-1) to establish the several clones including clone #1. These clones expressed the pluripotent gene markers and normal karyo type of chromosome. The embryoid body derived from clone#1 to differentiate cardiac cells included the HCN4-GFP positive cells at 5% out of total human ES cells. HCN4-GFP positive cells expressed cardiac contractile proteins and HCN4 channels. HCN4-GFP positive cells expressed the several ion channels being responsible for their automaticity. The Ca transient derived from the aggregation of HCN4-GFP positive cells propagated into the HL-1 atrial cell-sheet. Taken together, we establish the human ES cells harboringHCN4-GFP BAC vector and successfully isolate the HCN4-GFP positive pacemakingcells.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (39 results)

All 2013 2012 2011 Other

All Journal Article (28 results) (of which Peer Reviewed: 7 results) Presentation (8 results) Book (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Transplantation of freshly isolated adipose tissue-derived regenerative cells enhances angiogenesis in a murine model of hind limb ischemia2013

    • Author(s)
      Harada Y, Yamamoto Y, Tsujimoto S,Matsugami H, Yoshida A, Hisatome I.
    • Journal Title

      Biomed Res

      Volume: 34(1) Pages: 23-9

    • NAID

      130004470831

    • Related Report
      2012 Final Research Report
  • [Journal Article] Heterochromatin protein 1γ overexpression in P19 embryonal carcinoma cells elicits spontaneous differentiation into the three germ layers2013

    • Author(s)
      Morikawa K, Ikeda N, Hisatome I, Shirayoshi Y
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 431(2) Pages: 225-31

    • Related Report
      2012 Final Research Report
  • [Journal Article] A vasodilating β1 blocker celiprolol inhibits muscular release of uric acid precursor in patients with essential hypertension.2013

    • Author(s)
      Mizuta E, Utami SB, Ohtahara A, Endo S, Mishima M, Hasegawa A, Yamada K, Kato M, Yamamoto K, Ogino K, Ninomiya H, Miyazaki S, Hamada T, Taniguchi SI, Cheng J, Hisatome I.
    • Journal Title

      Horm Metab Res.

      Volume: 45(1) Pages: 69-73

    • Related Report
      2012 Final Research Report
  • [Journal Article] Heterochromatin protein 1γ overexpression in P19 embryonal carcinoma cells elicits spontaneous differentiation into the three germ layers.2013

    • Author(s)
      Morikawa K, Ikeda N, Hisatome I, Shirayoshi Y.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 431(2) Issue: 2 Pages: 225-31

    • DOI

      10.1016/j.bbrc.2012.12.128

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transplantation of freshly isolated adipose tissue-derived regenerative cells enhances angiogenesis in a murine model of hind limb ischemia.2013

    • Author(s)
      Harada Y
    • Journal Title

      Biomed Res.

      Volume: 34(1) Pages: 23-29

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of Hyperpolarization-Activated Current If on Robustness of Sinoatrial Node Pacemaking: theoretical study on influence of intracellular Na+ concentration.2013

    • Author(s)
      Kurata Y
    • Journal Title

      Am J Physiol Heart Circ Physiol.

      Volume: 掲載予定

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stabilization of Kv1.5 channel protein by bepridil through its action as a chemical chaperone2012

    • Author(s)
      Suzuki S, Kurata Y, Li P, Notsu T, Hasegawa A, Ikeda N, Kato M, Miake J, Sakata S, Shiota G, Yoshida A, Ninomiya H, Higaki K, Yamamoto K, Shirayoshi Y, Hisatome I.
    • Journal Title

      Eur J Pharmacol.

      Volume: 696(1-3) Pages: 28-34

    • NAID

      10027704706

    • Related Report
      2012 Final Research Report
  • [Journal Article] Electrophysiological properties of prion-positive cardiac progenitors derived from murine embryonic stem cells.2012

    • Author(s)
      Fujii H, Ikeuchi Y, Kurata Y, Ikeda N, Bahrudin U, Li P, Nakayama Y, Endo R, Hasegawa A, Morikawa K, Miake J,Yoshida A, Hidaka K, Morisaki T, Ninomiya H, Shirayoshi Y, Yamamoto K, Hisatome I.
    • Journal Title

      Circ J.

      Volume: 76(12) Pages: 2875-83

    • NAID

      10031126061

    • Related Report
      2012 Final Research Report
  • [Journal Article] Nohara R. Proinflammatory cytokine activation is linked to apoptotic mediator, soluble Fas level in patients with chronic heart failure2012

    • Author(s)
      Kinugawa T, Kato M, Yamamoto K, Hisatome I
    • Journal Title

      Int Heart J

      Volume: 53(3) Pages: 182-6

    • Related Report
      2012 Final Research Report
  • [Journal Article] Effects of cilnidipine on serum uric acid level and urinary nitrogen monoxide excretion in patients with hypertension.2012

    • Author(s)
      Hamada T, Yamada K, Mizuta E, Watanabe A, Osaki T, Ishida K, HasegawaA, Sakata S, Mishima M, Ogino K, Nosaka Y, Miyazaki S, Ohtahara A, Ninomiya H, Kato M, Yoshida A, Taniguchi S, Yamamoto K, Hisatome I.
    • Journal Title

      Clin Exp Hypertens

      Volume: 34(7) Pages: 470-3

    • Related Report
      2012 Final Research Report
  • [Journal Article] Roles of sarcoplasmic reticulum Ca2+ cycling and Na+/Ca2+ exchanger in sinoatrial node pacemaking: insights from bifurcation analysis of mathematical models2012

    • Author(s)
      Kur a t a Y, Hisatome I, Shibamoto T.
    • Journal Title

      Am J Physiol Heart Circ Physiol

      Volume: 302(11)

    • Related Report
      2012 Final Research Report
  • [Journal Article] Udin Bahrudin Carbohydrate diet links to higher risk of significant coronary artery disease in young Indonesian patients Cardiometabolic Investigation study2012

    • Author(s)
      Sugiri, Sefri Noventi, Ichiro Hisatome
    • Journal Title

      Biomedical Research

      Volume: 23(2) Pages: 159-165

    • Related Report
      2012 Final Research Report
  • [Journal Article] Electrophysiological properties of prion-positive cardiac progenitors derived from murine embryonic stem cells.2012

    • Author(s)
      Fujii H
    • Journal Title

      Circ J.

      Volume: 76(12) Pages: 2875-2883

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Roles of sarcoplasmic reticulum Ca2+ cycling and Na+/Ca2+ exchanger in sinoatrial node pacemaking: Insights from bifurcation analysis of mathematical models.2012

    • Author(s)
      Kurata Y
    • Journal Title

      American Journal of Physiology (Heart Circ Physiol)

      Volume: 302 Issue: 11 Pages: H2285-H2300

    • DOI

      10.1152/ajpheart.00221.2011

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reciprocal Control of hERG Stability by Hsp70 and Hsc70 with Implication for Restoration of LQT2 Mutant Stability2011

    • Author(s)
      Peili Li, Haruaki Ninomiya, Yasutaka Kurata, Masaru Kato, Junichiro Miake, Yasutaka Yamamoto, Osamu Igawa, Akira Nakai, Katsumi Higaki, Futoshi Toyoda, Jie Wu, Minoru Horie, Hiroshi Matsuura, Akio Yoshida, Yasuaki Shirayoshi, Masayasu Hiraoka, Ichiro Hisatome.
    • Journal Title

      Circ Res.

      Volume: 108(4) Pages: 458-68

    • NAID

      130002130408

    • Related Report
      2012 Final Research Report
  • [Journal Article] Transcriptional activation of SAP97 by HSF-1 stabilizes Kv1.5 in HL-1 cells2011

    • Author(s)
      YK Ting, K Morikawa, Y Kurata, PL Li, U Bahrudin, E Mizuta, M Kato,J Miake, Y Yamamoto, A Yoshida, M Murata, T Inoue, A Nakai, G Shiota, K Higaki, E Nanba, H Ninomiya, Y Shirayoshi, I Hisatome.
    • Journal Title

      Br J Pharmacol

      Volume: 162(8) Pages: 1832-1842

    • Related Report
      2012 Final Research Report
  • [Journal Article] Cytosolic Phospholipase A2{alpha} Contributes to Blood Pressure Increases and Endothelial Dysfunction Under Chronic NO Inhibition2011

    • Author(s)
      Tanaka K, Yamamoto Y, Ogino K, Tsujimoto S, Saito M, Uozumi N, Shimizu T, Hisatome I.
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 31(5) Pages: 1133-8

    • Related Report
      2012 Final Research Report
  • [Journal Article] Chemical chaperone therapy: chaperone effect on mutant enzyme and cellular pathophysiology in β-galactosidase deficiency2011

    • Author(s)
      Higaki K, Li L, Bahrudin U, Okuzawa S, Takamura A, Yamamoto K, Adachi K, Paraguison RC, Takai T, Ikehata H, Tominaga L, Hisatome I, Iida M, Ogawa S, Matsuda J, Ninomiya H, Sakakibara Y, Ohno K, Suzuki Y, Nanba E.
    • Journal Title

      Hum Mutat

      Volume: 32(7) Pages: 843-852

    • Related Report
      2012 Final Research Report
  • [Journal Article] Disrupted plasma membrane localization of equilibrative nucleoside transporter 2 in the chemoresistance of human pancreatic cells to gemcitabine (dFdCyd)2011

    • Author(s)
      16. Nishio R, Tsuchiya H, Yasui T, Matsuura S, Kanki K, Kurimasa A,Hisatome I, Shiota G.
    • Journal Title

      Cancer Sci

      Volume: 102(3) Pages: 622-9

    • Related Report
      2012 Final Research Report
  • [Journal Article] c-Jun N-terminal kinase activation by oxidative stress suppresses retinoid signaling through proteasomal degradation of retinoic acid receptor α protein in hepatic cells.2011

    • Author(s)
      Hoshikawa Y, Kanki K, Ashla AA, Arakaki Y, Azumi J, Yasui T, Tezuka Y, Matsumi Y, Tsuchiya H, Kurimasa A, Hisatome I, Hirano T, Fujimoto J, Kagechika H, Shomori K, Ito H, Shiota G.
    • Journal Title

      Cancer Sci.

      Volume: 120(5) Pages: 934-41

    • Related Report
      2012 Final Research Report
  • [Journal Article] Reactive oxygen species and NADPH oxidase 4 induced by transforming growth factor β1 are the therapeutic targets of polyenylphosphatidylcholine in the suppression of human hepatic stellate cell activation2011

    • Author(s)
      Ikeda R, Ishii K, Hoshikawa Y, Azumi J, Arakaki Y, Yasui T, Matsuura S, Matsumi Y, Kono Y, Mizuta Y, Kurimasa A, Hisatome I, Friedman SL, Kawasaki H, Shiota G.
    • Journal Title

      Inflamm Res

      Volume: 60(6) Pages: 597-604

    • Related Report
      2012 Final Research Report
  • [Journal Article] Novel effects of extracts from poisonous mushrooms on expression and function of the human ether-a-go-go-related gene channel.2011

    • Author(s)
      Li P, Tanaka S, Ichiyanagi T, Ninomiya H, Ting Y, Utami SB, Aimi T, Shirayoshi Y, Miake J, Hisatome I.
    • Journal Title

      Biol Pharm Bull

      Volume: 34(9) Pages: 1474-80

    • NAID

      130001872443

    • Related Report
      2012 Final Research Report
  • [Journal Article] Impairment of ubiquitin-proteasome system by E334K cMyBPC modifies channel proteins, leading to electrophysiological dysfunction2011

    • Author(s)
      Bahrudin U, Morikawa K, Takeuchi A, Kurata Y, Miake J, Mizuta E, Adachi K, HigakiK, Yamamoto Y, Shirayoshi Y, Yoshida A, Kato M, Yamamoto K, Nanba E, Morisaki H, Morisaki T, Matsuoka S, Ninomiya H, Hisatome I.
    • Journal Title

      J Mol Biol

      Volume: 413(4) Pages: 857-78

    • Related Report
      2012 Final Research Report
  • [Journal Article] Enhancing effects of salicylate on quinidine-induced block of human wild type and LQT3 related mutant cardiac Na+ channels2011

    • Author(s)
      Urashima T, Kurata Y, Miake J, Kato M, Ogura K, Yano A, Adachi M, Tanaka Y, Yamada K, Hamada T, Mizuta E, Kuwabara M, Kato M, Yamamoto Y, Ogino K, Yoshida A, Shirayoshi Y, Hisatome I.
    • Journal Title

      Biomed Res

      Volume: 32(5) Pages: 303-12

    • NAID

      130004724056

    • Related Report
      2012 Final Research Report
  • [Journal Article] Enhancing effects of salicylate on quinidine-induced block of human wild type and LQT3 related mutant cardiac Na+ channels2011

    • Author(s)
      浦島直ら
    • Journal Title

      Biomedical Research

      Volume: 32 Issue: 5 Pages: 303-312

    • DOI

      10.2220/biomedres.32.303

    • NAID

      130004724056

    • ISSN
      0388-6107, 1880-313X
    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] エピジェネティック因子HP1γを介した心筋及びペースメーカ細胞新規誘導法の開発2011

    • Author(s)
      森川久未ら
    • Journal Title

      心電図

      Volume: 31(4) Pages: 408-416

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] AMP deaminase 3 plays a critical role in remote reperfusion lung injury.

    • Author(s)
      Li P, Ogino K, Hoshikawa Y, Morisaki H, Toyama K, Morisaki T, Morikawa K, Ninomiya H, Yoshida A, Hashimoto K, Shirayoshi Y, Hisatome I.
    • Journal Title

      Biochem Biophys Res Commun.

    • Related Report
      2012 Final Research Report
  • [Journal Article] Effect of Hyperpolarization-Activated Current If on Robustness of Sinoatrial Node Pacemaking: theoretical study on influence of intracellular Na+ concentration

    • Author(s)
      Kurata Y, Biochem Biophys Res Commun. (in press)Hisatome I, Tanida M, Shibamoto T.
    • Journal Title

      Am J Physiol Heart Circ Physiol

    • Related Report
      2012 Final Research Report
  • [Presentation] Functional integration of HCN4 positive cardiac pacemaking cells derived from mouse embryonicstem cells with recipient cardiomyocytes2013

    • Author(s)
      Kumi Morikawa
    • Organizer
      第77回日本循環器学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] Intracelluar Ca2+ handling regulates the automaticity of HCN4-GFP(+) pacemaking cells derived frommurine ES cells during cardiac differentiation2013

    • Author(s)
      Udin Bahrudin
    • Organizer
      第77回日本循環器学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] Elecrophysiological and molecular biological properties of prion-positive cardiac progenitors derived from muirne embryonic stem cells2013

    • Author(s)
      Ysutaka Kurata
    • Organizer
      第77回日本循環器学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] Functional integration of HCN4 positive cardiac pacemaking cells derived from mouse embryonic stem cells with recipient cardiomyocytes2013

    • Author(s)
      Kumi Morikawa
    • Organizer
      第77回日本循環器学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Intracelluar Ca2+ handling regulates the automaticity of HCN4-GFP(+) pacemaking cells derived from murine ES cells during cardiac differentiation2013

    • Author(s)
      Udin Bahrudin
    • Organizer
      第77回日本循環器学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Elecrophysiological and molecular biological properties of prion-positive cardiac progenitors derived from muirne embryonic stem cells.2013

    • Author(s)
      Ysutaka Kurata
    • Organizer
      第77回日本循環器学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2012 Annual Research Report
  • [Presentation] The Epigenetic Factor HP1 Facilitates Cardiac Differentiation of P19 Embryonal Carcinoma Cell2011

    • Author(s)
      森川久未
    • Organizer
      4th Asia Pacific Heart Rhythm Society Scientific Session
    • Place of Presentation
      福岡シーホークホテル(福岡市)
    • Related Report
      2011 Research-status Report
  • [Presentation] HCN4-GFPノックイン胚性幹細胞由来ペースメーカ細胞の電気性学的解析2011

    • Author(s)
      藤井裕士ら
    • Organizer
      第99回日本循環器学会中国地方会
    • Place of Presentation
      海峡メッセ(下関市)
    • Related Report
      2011 Research-status Report
  • [Book] Heart View2013

    • Author(s)
      久留一郎
    • Total Pages
      5
    • Publisher
      メディカルビュー社
    • Related Report
      2012 Annual Research Report
  • [Patent(Industrial Property Rights)] 安全性の高い再生医療技術の確立2013

    • Inventor(s)
      久留一郎
    • Industrial Property Rights Holder
      鳥取大学
    • Filing Date
      2013-01-30
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] 安全性の高い再生医療技術の確立2013

    • Inventor(s)
      久留一郎
    • Industrial Property Rights Holder
      久留一郎
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-01-30
    • Related Report
      2012 Annual Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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