Arrhythmogenic consequences of stem cell therapy for cardiac regeneration

A third of the patients that survive a myocardial infarction develop heart failure for which no effective treatment exists. Stem cell therapy could be a possible solution by regeneration of the myocardium. However, the possible electrophysiological effects of interactions between stem cells and cardiomyocytes are not fully understood and there are concerns for arrhythmias. Previous research has focused on optimizing the efficacy of cell therapy but little attention has been dedicated to elucidate potential pro-arrhythmic consequences. These consequences are however not less relevant than the efficacy of therapy itself, because lethal arrhythmias negate the therapy to succeed. In this thesis we investigated the potential arrhythmogenic consequences of cardiac regenerative stem cell therapy. It was aimed to understand how interactions between stem cells and cardiomyocytes could form a pro-arrhythmic substrate.
The results show that administered (stem) cells can lead to the formation of a pro-arrhythmic substrate. The results were obtained from experiments in which stem cells were co-cultured with cardiomyocytes but also from experiments where we used a mouse and pig animal model of heart failure. Based on the obtained results, I suggest a future perspective in which cardiac regeneration will be mediated by stimulating the endogenous regeneration mechanisms by making use of key factors of the stem cell secretome. For the development of a therapy in the form of a "ready-to-use" product, further research into these key factors is necessary. In doing so, any arrhythmogenic effects must be taken into account because they can strongly influence the success of therapy.