Journal Article Modelling Torsade de Pointes arrhythmias in vitro in 3D human iPS cell-engineered heart tissue

Kawatou, Masahide  ,  Masumoto, Hidetoshi  ,  Fukushima, Hiroyuki  ,  Morinaga, Gaku  ,  Sakata, Ryuzo  ,  Ashihara, Takashi  ,  Yamashita, Jun K.

82017-10-20 , Springer Nature
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.
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.

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