Key result
LQT1 cardiac microtissues exhibit prolonged field potential duration versus wild-type controls, recapitulating long QT syndrome.
Why the study?
Strategies to mature hiPSC-CMs and comprehensive systems recapitulating heart complexity are required to better capture adult phenotypes of cardiac ion channel diseases.
3D cardiac microtissues derived from hiPSCs successfully recapitulate the electrical phenotype of long-QT syndrome type 1, providing a scalable in vitro tool for drug screening and disease modeling.
May enhance hiPSC-based LQT1 modeling with multicellular systems; leaves open adult phenotype capture and clinical translation.
BACKGROUND: Human induced pluripotent stem cells (hiPSCs) and their derivative cardiomyocytes (hiPSC-CMs) have been successfully used to study the electrical phenotype of cardiac ion channel diseases. However, strategies to mature CMs and more comprehensive systems recapitulating the heart complexity are required to advance our ability to capture adult phenotypes. METHODS: We differentiated wild-type (WT) and long QT syndrome type 1 (LQT1) hiPSCs into CMs, endothelial cells and cardiac fibroblasts. The three cell types were combined to form three-dimensional (3D) spheroids, termed "cardiac microtissues" (cMTs) and the electrophysiological properties were measured using 96-well multi-electrode arrays. RESULTS: LQT1 cMTs displayed prolonged field potential duration compared to WT controls, thus recapitulating the typical feature of LQTS. Isoprenaline caused a positive chronotropic effect on both LQT1 and WT cMTs. The 96-well multi-electrode array format proved suitable to detect electrical changes directly in the 3D tissues. CONCLUSIONS: 3D hiPSC cMTs are a scalable tool that can be used to identify LQT electrical hallmarks and drug responses. We anticipate this tool can be adopted by pharmaceutical companies to screen cardio-active compounds.
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Giacomelli et al. (2021) studied Long QT syndrome type 1. LQT1 hiPSC-derived cardiac microtissues vs. Wild-type (WT) cardiac microtissues was evaluated on Field potential duration. LQT1 cardiac microtissues displayed prolonged field potential duration compared to wild-type controls, recapitulating the typical feature of long QT syndrome.
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