Simulations of the electrical activity of cardiomyocytes derived from human embrionic stem cells

In this thesis, a cellular automata based modelling software is developed for studying the electrical activation of cardiomyocytes. The mathematical models help to simulate and study different phenomena related to the cardiac activation. They enable flexible studies for healthy and unhealthy tissue and give a better understanding of the behaviour of the electrical propagation in the heart. The models which are implemented with a graphical user interface are easier to use for inexpert users. This makes these programs very helpful for educational purpose as well as valuable tools for research groups. Nowadays, one of the aspects of the research in the cardiac field is the stem cells. Cardiomyocytes derived from stem cells are being grown in the laboratories to be analysed and used in drug screening. The differentiation of the cells in a particular type is not straightforward. There can be several types of cardiac cells (ventricular, atrial or sinoatrial myocytes) in the same cell culture. Patch clamp is used to discern which types of cells were grown and microelectrodes arrays (MEA) are used to measure the electrical signals produced by the cultures. Patch clamp is costly and time consuming process to identify the cells. The main goal of this master thesis is to study the differences in the simulated electrograms (EGM) from the normal electrodes recordings when the type of cell is changed. If there are quantitative changes the EGM, it could be possible to know a priori which type of cardiomyocyte is present in the culture without having a patch clamp study. The model simulates the electrical activity of cell culture with a cellular automaton based on cardiomyocyte action potential and the conduction velocity curves. These curves are known as restitution curves of the cardiac tissue. It is also needed to model the geometry of the cell culture and the MEA electrodes. This geometry and its lead fields calculated with a finite difference model (FDM) are the inputs for the cellular automata. The cellular automata and the FDM model of the cell culture were successfully performed. The results show that there are differences in the EGM when the action potential of each type of cell is set in the model. The biggest difference is between the contractile cells and the pacemaker ones. The cells could be classified a priori with this study, but in the real life there are more factors that are included and not just one type of cell. There is a need to try in vitro models to check this hypothesis.