Center for Quantitative Biology, Peking University, Beijing, 100871, China.
Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Sci Rep. 2020 Feb 19;10(1):2984. doi: 10.1038/s41598-020-59803-9.
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.
从人类诱导多能干细胞中开发更成熟的心肌细胞对于细胞移植和药物筛选至关重要。在之前的一项研究中,我们描述了一个平台,在该平台上,源自人类诱导多能干细胞(hiPSC-CMs)的心肌细胞形成三维自组织组织环。在这些环中,动作电位的传播波会自发地长时间起源和传播。为了了解这些波的动态行为,我们开发了一个用于此类环中电信号循环的数学模型。通过使用动作电位和传导速度的恢复曲线,我们证明了稳定循环和速度依赖性特征的基础机制。分析结果与自组织组织环中传播波的起源、传播和长期行为的实验数据吻合较好。传播波的理论分析也可以为心脏折返节律的分析提供参考。