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Analysis of Circulating Waves in Tissue Rings derived from Human Induced Pluripotent Stem Cells.

ABSTRACT: Developing more mature cardiomyocytes derived from human induced pluripotent stem cells is essential for cell transplantation and drug screening. In a previous study, we described a platform on which cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) formed three-dimensional self-organized tissue rings. Within these rings, traveling waves of action potentials spontaneously originate and propagate for a long time. In order to understand the dynamic behavior of these waves, we developed a mathematical model for the circulation of the electrical signal in such rings. By using the restitution curves of the action potential and the conduction velocity we demonstrated the mechanisms underlying the steady circulation and the features dependent on velocity. The analytic result agreed well with the experimental data in the origination, propagation, and long-term behavior of traveling waves within self-organized tissue rings. The theoretical analysis of traveling waves may also provide a reference to the analysis of reentrant rhythms in hearts.

SUBMITTER: Zhang L

PROVIDER: S-EPMC7031392 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Analysis of Circulating Waves in Tissue Rings derived from Human Induced Pluripotent Stem Cells.

Zhang Lu L Li Junjun J Liu Li L Tang Chao C

Scientific reports 20200219 1

Developing more mature cardiomyocytes derived from human induced pluripotent stem cells is essential for cell transplantation and drug screening. In a previous study, we described a platform on which cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) formed three-dimensional self-organized tissue rings. Within these rings, traveling waves of action potentials spontaneously originate and propagate for a long time. In order to understand the dynamic behavior of these wave ...[more]

PMID: 32076031

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Project description:Background Optogenetics, using light-sensitive proteins, emerged as a unique experimental paradigm to modulate cardiac excitability. We aimed to develop high-resolution optogenetic approaches to modulate electrical activity in 2- and 3-dimensional cardiac tissue models derived from human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes. Methods and Results To establish light-controllable cardiac tissue models, opsin-carrying HEK293 cells, expressing the light-sensitive cationic-channel CoChR, were mixed with hiPSC-cardiomyocytes to generate 2-dimensional hiPSC-derived cardiac cell-sheets or 3-dimensional engineered heart tissues. Complex illumination patterns were designed with a high-resolution digital micro-mirror device. Optical mapping and force measurements were used to evaluate the tissues' electromechanical properties. The ability to optogenetically pace and shape the tissue's conduction properties was demonstrated by using single or multiple illumination stimulation sites, complex illumination patterns, or diffuse illumination. This allowed to establish in vitro models for optogenetic-based cardiac resynchronization therapy, where the electrical activation could be synchronized (hiPSC-derived cardiac cell-sheets and engineered heart tissue models) and contractile properties improved (engineered heart tissues). Next, reentrant activity (rotors) was induced in the hiPSC-derived cardiac cell-sheets and engineered heart tissue models through optogenetics programmed- or cross-field stimulations. Diffuse illumination protocols were then used to terminate arrhythmias, demonstrating the potential to study optogenetics cardioversion mechanisms and to identify optimal illumination parameters for arrhythmia termination. Conclusions By combining optogenetics and hiPSC technologies, light-controllable human cardiac tissue models could be established, in which tissue excitability can be modulated in a functional, reversible, and localized manner. This approach may bring a unique value for physiological/pathophysiological studies, for disease modeling, and for developing optogenetic-based cardiac pacing, resynchronization, and defibrillation approaches.

Dataset Information

Analysis of Circulating Waves in Tissue Rings derived from Human Induced Pluripotent Stem Cells.

Publications

Analysis of Circulating Waves in Tissue Rings derived from Human Induced Pluripotent Stem Cells.

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