Application of Human iPS Cell-Technologies to Arrhythmia Researches

Mitsushige Murata, Toru Egashira, Kojiro Yae, Shinsuke Yuasa, Keiichi Fukuda

Research output: Contribution to journalArticle

Abstract

The possibility of modeling human diseases has been a potential in regenerative medicine. Disease modeling especially using human induced pluripotent stem (hiPS) cell is highly applicable for the novel approaches to analyze genetic cardiovascular diseases. Although the inherited fatal arrhythmogenic diseases including long QT syndrome (LQTs) have been characterized by their clinical as well as genomic phenotypes, further investigations for elucidation of pathogenesis and development of tailor-maid therapy are highly desired. We generated hiPS cells from healthy volunteers or patients with LQTs by transfecting 4 reprogmming genes such as Oct3/4, Sox2, Klf4, and c-Myc. Stable iPS colonies were screened by immunostaining and RT-PCR of the various stem cell markers, and cardiac differentiation of hiPS cells were made by formation of embryoid bodies. Molecular characterization of hiPS-derived cardiomyocytes was investigated, and action potential was recorded using conventional microelectrode technique. Furthermore, drug sensitivity test was also performed by multi-electrode array systems. HiPS-derived cardiomyocytes of normal volunteers showed the similar characteristics to native cardiomyocytes on expression of cardiac specific-marker genes and electrophysiologic phenotypes. Notably, LQTs model using patient-specific iPS-derived cardiomyocytes showed the characteristic LQTs phenotype, comparing to healthy control, implicating that disease modeling using hiPS cells may play a crucial role for arrhythmia researches including disease mechanisms as well as development of new therapies.

Original languageEnglish
JournalJournal of Arrhythmia
Volume27
DOIs
Publication statusPublished - 2011

Fingerprint

Hip
Cardiac Arrhythmias
Cardiac Myocytes
Technology
Research
Phenotype
Healthy Volunteers
Embryoid Bodies
Long QT Syndrome
Induced Pluripotent Stem Cells
Inborn Genetic Diseases
Regenerative Medicine
Differentiation Antigens
Microelectrodes
Genes
Action Potentials
Cell Differentiation
Electrodes
Cardiovascular Diseases
Stem Cells

Keywords

  • arrythmias
  • hiPS cells
  • LQT

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Application of Human iPS Cell-Technologies to Arrhythmia Researches. / Murata, Mitsushige; Egashira, Toru; Yae, Kojiro; Yuasa, Shinsuke; Fukuda, Keiichi.

In: Journal of Arrhythmia, Vol. 27, 2011.

Research output: Contribution to journalArticle

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