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A novel approach to treat arrhythmias using embryonic stem-derived cardiac pacemaker cells

Research Project

Project/Area Number 14570653
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionNagoya University

Principal Investigator

LEE Jong-kook  Nagoya University, Research Institute of Environmental Medicine, Research Associate, 環境医学研究所, 助手 (60303608)

Co-Investigator(Kenkyū-buntansha) MORISAKI Takayuki  National Cardiovascular Center, Department of Bioscience, Director, バイオサイエンス部, 部長 (30174410)
HIDAKA Kyoko  National Cardiovascular Center, Department of Bioscience, Laboratory Chief, バイオサイエンス部, 室長 (00216681)
KODAMA Itsuo  Nagoya University, Research Institute of Environmental Medicine, Professor, 環境医学研究所, 教授 (30124720)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,600,000 (Direct Cost: ¥2,600,000)
KeywordsRegenerative medicine / Embryonic stem cell / Arrhythmia / Bio-pacemaker / ペースメーカー細胞
Research Abstract

We investigated the electrophysiological differentiation of embryonic stem (ES) cell-derived cardiac myocytes (ESCMs) during a long-term culture and electrical coupling with native myocytes. Nkx2.5-GFP knock-in murine ES cells were established by inserting GFP into Nkx2.5 allele. Embryoid bodies obtained with "hanging-drop" method were dispersed on day 10,and GFP-positive cells were isolated by FACS. ESCMs after the sorting were cultured for 21 days to record APs using patch-clamp technique. ESCMs were also cultured with neonatal mouse ventricular myocytes confluently on a dish with 64 unipolar electrodes (MED64) to examine their electrical coupling. ESCMs sorted as GFP-positive cells were 3-5% of total population. Most of the ESCMs (>95%) were immunopositive for cardiac troponin I. On 7-day after FACS,〜85% ESCMs showed continuous spontaneous beating (148±45bpm, n=20). APs at this stage had prominent pacemaker depolarization, slow upstroke phase, and long duration (max diastolic potential -48±2mV ; APD_<90> 95±15ms, n=5) like SA node cells. On 21-day, only 20% ESCMs showed spontaneous beating, and remaining 80% quiescent. APs of the quiescent cells had more negative resting membrane potential and shorter duration (-68±6mV and 38±2ms n=5) like atrial or ventricular myocytes. ESCMs co-cultured with neonatal ventricular myocytes on MED64 for 7 days showed synchronization of spontaneous excitation. Cardiac myocytes derived from Nkx2.5-GFP knock-in ES cells can differentiate into various types of cardiac cells including atrial cells, ventricular cells or SA node cells. They are able to form functional electrical coupling with native cardiac myocytes.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Hidaka K, Lee JK, Kim HS, Ihm CH, Iio A, Ogawa M, Nishikawa S, Kodama I, Morisaki T: "Chamber-specific Differentiation of Nkx2.5-positive Cardiac Precursor Cells from Murine Embryonic Stem Cells."FASEB Journal. 17(6). 740-742 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miwa K, Lee_JK, Hidaka K, Shi RQ, Morisaki T, Kodama I: "Optimal population of embryonic stem cells in "hanging drop"culture for in-vitro differentiation to cardiac myocytes"Environmental Medicine. 46(1). 92-94 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Lee JK, Hidaka K, Miwa K, Shi RQ, Itho G, Morisaki T, Kodama I: "Cardiac myocytes derived from Nkx2.5-GFP knock-in murine embryonic stem cell : Electrophysiological differentiation and coupling with native cardiac myocytes"Journal of Molecular and Cellular Cardiology. 34(10)(abstract). A24 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Lee JK, Hidaka K, Miwa K, Shi RQ, Zhang L, Morisaki T, Kodama I: "Cardiac Myocytes derive from Nkx2.5-GFP knock-in murine embryonic stem cell : electrophysiological differentiation and feasibility of transplantation"Circulation. 106(19)(abstract). II-68 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miwa K, Lee JK, Hidaka K, Shi R, Itoh G, Morisaki T, Kodama I.: "Paracrine factors from cultured cardiac cells promote differentiation of embryonic stem cells into cardiac myocytes."Environmental Medicine. 47. 45-47 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hidaka K, Lee JK, Kim HS, Ihm CH, Iio A, Ogawa M, Nishikawa S, Kodama I, Morisaki T.: "Chamber-specific Differentiation of Nkx2.5-positive Cardiac Precursor Cells from Murine Embryonic Stem Cells."FASEB Journal. 17(6). 740-742 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miwa K, Lee JK, Hidaka K, Shi RQ, Morisaki T, Kodama I.: "Optimal population of embryonic stem cells in "hanging drop" culture for in-vitro differentiation to cardiac myocytes"Environmental Medicine. 46(1). 92-94 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Lee JK, Hidaka K, Miwa K, Shi RQ, Itho G, Morisaki T, Kodama I.: "Cardiac myocytes derived from Nkx2.5-GFP knock-in murine embryonic stem cell : Electrophysiological differentiation and coupling with native cardiac myocytes"Journal of Moledula and Cellular Cardiology. 34(10). A24(abstract) (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Lee JK, Hidaka K, Miwa K, Shi RQ, Itho G, Morisaki T, Kodama I.: "Cardiac myocytes derived from Nkx2.5-GFP knock-in murine embryonic stem cell : Electrophysiological differentiation and coupling with native cardiac myocytes."Circulation. 106(19). II-68(abstract)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miwa K, Lee JK, Hidaka K, Shi R, Itoh G, Morisaki T, Kodama I.: "Paracrine factors from cultured cardiac cells promote differentiation of embryonic stem cells into cardiac myocytes."Environmental Medicine. 47. 45-47 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hidaka K, Lee JK, Kim HS, Ihm CH, Iio A, Ogawa M, Nishikawa S, Kodama I, Morisaki T: "Chamber-specific Differentiation of Nkx2.5-positive Cardiac Precursor Cells from Murine Embryonic Stem Cells"FASEB Journal. Express article Feb 19, 2003. fj.02-0104 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miwa K, Lee JK, Hidaka K, Shi RQ, Morisaki T, Kodama I: "Optimal population of embryonic stem cells in "hanging drop" culture for in-vitro differentiation to cardiac myocytes"Environmental Medicine. 46(1). 92-94 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Lee JK, Hidaka K, Miwa K, Shi RQ, Itho G, Morisaki T, Kodama I: "Cardiac myocytes derived from Nkx2.5-GFP knock-in murine embryonic stem cell : Electrophysiological differentiation and coupling with native cardiac myocytes"Journal of Molecular and Cellular Cardiology. 34(10)(abstract). A24 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Lee JK, Hidaka K, Miwa K, Shi RQ, Zhang L, Morisaki T, Kodama I: "Cardiac Myocytes derive from Nkx2.5-GFP knock-in murine embryonic stem cell : electrophysiological differentiation and feasibility of transplantation"Circulation. 106(19)(abstract). II-68 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miwa K, Lee JK, Hidaka K, Shi R, Itoh G, Morisaki T, Kodama I.: "Paracrine factors from cultured cardiac cells promote differentiation of embryonic stem cells into cardiac myocytes"Environmental Medicine. 47. 45-47 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hidaka K, Lee JK, Kim HS, Ihim CH, Iio A, Ogawa M, Nishikawa S. Kodama I, Morisaki T: "Chamber-specific Differentiation of Nkx2.5-positive Cardiac Precursor Cells from Murine Embryonic Stem Cells"FASEB Journal. Express article Feb 19, 2003. fj-02-0104 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miwa K, Lee JK, Hidaka K, Shi RQ, Morisaki T, Kodama I: "Optimal population of embryonic in "hanging drop" culture for in-vitro differentiation to cardiac myocytes"Environmental Medicine. 46(1). 92-94 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 李鍾国, 児玉逸雄: "遺伝子導入による心筋電気特性の制御-不整脈の遺伝子治療は可能か?"医学のあゆみ. 200(9). 769-774 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsuji Y, Opthof T, Yasui K, Inden Y, Takemura H, Niwa N, Lu Z, Lee JK, Honjo H, Kamiya K, Kodama I: "Ionic mechanisms of acquired QT prolongation and torsades de pointes in rabbits with chronic complete atrioventricular block"Circulation. 106(15). 2012-2018 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Lee JK, Hidaka K, Miwa K, ShiRQ, Zhang L, Morisaki T, Kodama I: "Cardiac Myocytes derive from Nkx2.5-GFP knock-in murine embryonic stem cell : electrophysiological differentiation and feasibility of transplantation"Circulation. 106(19). II-68(abstract) (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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