ID | 63390 |
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著者 |
Saito, Yukihiro
Department of Cardiovascular Medicine, Okayama University Hospital
Nakamura, Kazufumi
Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
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Yoshida, Masashi
Department of Chronic Kidney Disease and Cardiovascular Disease, Dentistry, and Pharmaceutical Science, Okayama University Graduate School of Medicine
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Sugiyama, Hiroki
Department of Internal Medicine, Okayama Saiseikai General Hospital
Akagi, Satoshi
Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
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Miyoshi, Toru
Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
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Morita, Hiroshi
Department of Cardiovascular Therapeutics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
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Ito, Hiroshi
Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
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抄録 | Background The number of patients with bradyarrhythmia and the number of patients with cardiac pacemakers are increasing with the aging population and the increase in the number of patients with heart diseases. Some patients in whom a cardiac pacemaker has been implanted experience problems such as pacemaker infection and inconvenience due to electromagnetic interference. We have reported that overexpression of HCN channels producing a pacemaker current in mouse embryonic stem cell-derived cardiomyocytes showed enhanced pacing function in vitro and in vivo. The aim of this study was to determine whether HCN4 overexpression in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) can strengthen the pacing function of the cells. Methods Human HCN4 was transduced in the AAVS1 locus of human induced pluripotent stem cells by nucleofection and HCN4-overexpressing iPSC-CMs were generated. Gene expression profiles, frequencies of spontaneous contraction and pacing abilities of HCN4-overexpressing and non-overexpressing iPSC-CMs in vitro were compared. Results HCN4-overexpressing iPSC-CMs showed higher spontaneous contraction rates than those of non-overexpressing iPSC-CMs. They responded to an HCN channel blocker and beta adrenergic stimulation. The pacing rates against parent iPSC line-derived cardiomyocytes were also higher in HCN4-overexpressing iPSC-CMs than in non-overexpressing iPSC-CMs. Conclusions Overexpression of HCN4 showed enhancement of I-f current, spontaneous firing and pacing function in iPSC-CMs. These data suggest this transgenic cell line may be useful as a cardiac pacemaker.
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キーワード | Hyperpolarization-activated cyclic nucleotide-gated potassium channel 4
Human induced pluripotent stem cell-derived cardiomyocytes
Pacing
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発行日 | 2022-04-01
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出版物タイトル |
STEM Cell Research & Therapy
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巻 | 13巻
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号 | 1号
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出版者 | BMC
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開始ページ | 141
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ISSN | 1757-6512
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © The Author(s) 2022.
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論文のバージョン | publisher
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PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.1186/s13287-022-02818-y
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ライセンス | http://creativecommons.org/licenses/by/4.0/.
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