The team of professor Chao Tang and Li liu published ‘Analysis of circulating Waves in tissue Rings derived from Human induced pluripotent Stem cells’ and ‘Circulating re-entrant waves promote maturation of hiPSC-derived cardiomyocytes in self-organized tissue ring’in Scientific Reports and Communications Biology respectively on February 19 and March 13, 2020. These papers focused on the cardiomyocytes derived from human induced pluripotent stem cells, and demonstrated the traveling waves are associated with structural and functional maturation of the cardiomyocytes. At the same time, by using the corresponding mathematical model, the dynamic characteristics of traveling waves are also analyzed.
Directed differentiation methods allow acquisition of high-purity cardiomyocytes differentiated from human induced pluripotent stem cells. However, their immaturity characteristic limits their application for drug screening and regenerative therapy. The rapid electrical pacing of cardiomyocytes has been used for efficiently promoting the maturation of cardiomyocytes. Therefore, we described a simple device in modified culture plate on which human induced pluripotent stem cells derived cardiomyocytes can form three-dimensional self-organized tissue rings. Using calcium imaging, we show that within the ring, traveling waves of action potential spontaneously originated and ran robustly. Meanwhile, self-organized tissue rings with traveling waves show higher maturation.
In addition, we developed a mathematical model for the circulation of the electrical signal in such rings based on the HH model and cable equations. Through a lot of theoretical simulations and mathematical analysis, we demonstrated the mechanisms underlying the steady circulation, the effect of gap junctions on stability of traveling waves, and the key factor affecting the speed of traveling waves. Our results not only offer a supplementary approach to improve the maturity of cardiomyocytes derived from human induced pluripotent stem cells, but also provide a reference to the analysis of reentrant rhythms in hearts.
