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.
Highlights
We demonstrated a variety of traveling waves which arose spontaneously and maintained for a long time in self-organized tissue rings. These spontaneously generated waves dramatically promoted the maturity of hiPSC derived cardiomyocytes, enhanced cardiac gene expression, and improved the Ca2+-handling properties[6]
In this work, based on the computational simulation and the theoretical analysis, we demonstrate that the speed of electrical signal propagation depend on the difference in electrical potential and the time available for a cell to recover after the preceding excitation
We find that circulating traveling waves can be sustained or lost depending on the derivative of the action potential restitution function
Summary
Excitable chemical media in annular geometries can maintain circulating waves once they are initiated[32,33]. Because of heterogeneities it is difficult to produce persistent circulating waves in a ring of cardiac cells. In many idealized settings the conservation of circulating waves is expected, in more realistic situations there is no priori reason to expect conservation of the numbers of circulating waves.
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