Application of Human iPS Cell-Technologies to Arrhythmia Researches

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

研究成果: Article査読

抄録

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.

本文言語English
ジャーナルjournal of arrhythmia
27
DOI
出版ステータスPublished - 2011

ASJC Scopus subject areas

  • 循環器および心血管医学

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