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Title: Modelling Torsade de Pointes arrhythmias in vitro in 3D human iPS cell-engineered heart tissue
Authors: Kawatou, Masahide
Masumoto, Hidetoshi  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-4059-2827 (unconfirmed)
Fukushima, Hiroyuki
Morinaga, Gaku
Sakata, Ryuzo
Ashihara, Takashi
Yamashita, Jun K.
Author's alias: 川東, 正英
升本, 英利
福島, 弘之
森永, 学
坂田, 隆造
芦原, 貴司
山下, 潤
Keywords: Experimental models of disease
Stem-cell biotechnology
Issue Date: 20-Oct-2017
Publisher: Springer Nature
Journal title: Nature Communications
Volume: 8
Thesis number: 1078
Abstract: Torsade de Pointes (TdP) is a lethal arrhythmia that is often drug-induced, thus there is an urgent need for development of models to test or predict the drug sensitivity of human cardiac tissue. Here, we present an in vitro TdP model using 3D cardiac tissue sheets (CTSs) that contain a mixture of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and non-myocytes. We simultaneously monitor the extracellular field potential (EFP) and the contractile movement of the CTSs. Upon treatment with IKr channel blockers, CTSs exhibit tachyarrhythmias with characteristics of TdP, including both a typical polymorphic EFP and meandering spiral wave re-entry. The TdP-like waveform is predominantly observed in CTSs with the cell mixture, indicating that cellular heterogeneity and the multi-layered 3D structure are both essential factors for reproducing TdP-like arrhythmias in vitro. This 3D model could provide the mechanistic detail underlying TdP generation and means for drug discovery and safety tests.
Description: ヒトiPS細胞から3次元的な心臓組織を作製し、致死性不整脈の複雑な特徴を培養下に再現することに成功. 京都大学プレスリリース. 2017-10-25.
Rights: © The Author(s) 2017
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
URI: http://hdl.handle.net/2433/227712
DOI(Published Version): 10.1038/s41467-017-01125-y
PubMed ID: 29057872
Related Link: https://www.kyoto-u.ac.jp/ja/research-news/2017-10-25-0
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