ハットリ　フミユキ   HATTORI FUMIYUKI   服部　文幸    所属   関西医科大学  iPS・幹細胞再生医学講座    職種   研究教授
論文種別	症例報告
言語種別	英語
査読の有無	その他(不明)
表題	Disease characterization using LQTS-specific induced pluripotent stem cells.
掲載誌名	正式名：Cardiovascular research 略　 称：Cardiovasc Res ISSNコード：1755324500086363
巻・号・頁	95(4),pp.419-29
著者・共著者	Egashira Toru, Yuasa Shinsuke, Suzuki Tomoyuki, Aizawa Yoshiyasu, Yamakawa Hiroyuki, Matsuhashi Tomohiro, Ohno Yohei, Tohyama Shugo, Okata Shinichiro, Seki Tomohisa, Kuroda Yusuke, Yae Kojiro, Hashimoto Hisayuki, Tanaka Tomofumi, Hattori Fumiyuki, Sato Toshiaki, Miyoshi Shunichiro, Takatsuki Seiji, Murata Mitsushige, Kurokawa Junko, Furukawa Tetsushi, Makita Naomasa, Aiba Takeshi, Shimizu Wataru, Horie Minoru, Kamiya Kaichiro, Kodama Itsuo, Ogawa Satoshi, Fukuda Keiichi
発行年月	2012/09
概要	AIMS:Long QT syndrome (LQTS) is an inheritable and life-threatening disease; however, it is often difficult to determine disease characteristics in sporadic cases with novel mutations, and more precise analysis is necessary for the successful development of evidence-based clinical therapies. This study thus sought to better characterize ion channel cardiac disorders using induced pluripotent stem cells (iPSCs).METHODS AND RESULTS:We reprogrammed somatic cells from a patient with sporadic LQTS and from controls, and differentiated them into cardiomyocytes through embryoid body (EB) formation. Electrophysiological analysis of the LQTS-iPSC-derived EBs using a multi-electrode array (MEA) system revealed a markedly prolonged field potential duration (FPD). The IKr blocker E4031 significantly prolonged FPD in control- and LQTS-iPSC-derived EBs and induced frequent severe arrhythmia only in LQTS-iPSC-derived EBs. The IKs blocker chromanol 293B did not prolong FPD in the LQTS-iPSC-derived EBs, but significantly prolonged FPD in the control EBs, suggesting the involvement of IKs disturbance in the patient. Patch-clamp analysis and immunostaining confirmed a dominant-negative role for 1893delC in IKs channels due to a trafficking deficiency in iPSC-derived cardiomyocytes and human embryonic kidney (HEK) cells.CONCLUSIONS:This study demonstrated that iPSCs could be useful to characterize LQTS disease as well as drug responses in the LQTS patient with a novel mutation. Such analyses may in turn lead to future progress in personalized medicine.
DOI	10.1093/cvr/cvs206
PMID	22739119