Stem cells can form gap junctions with cardiac myocytes and exert pro-arrhythmic effects

Abstract

Stem cell therapy has been suggested to be a promising option for regeneration of injured myocardium, for example following a myocardial infarction. For clinical use cell-based therapies have to be safe and applicable and are aimed to renovate the architecture of the heart. Yet for functional and coordinated activity synchronized with the host myocardium stem cells have to be capable of forming electrical connections with resident cardiomyocytes. In this paper we discuss whether stem cells are capable of establishing functional electrotonic connections with cardiomyocytes and whether these may generate a risk for arrhythmias. Application of stem cells in the clinical setting with outcomes concerning arrhythmogenic safety and future perspectives will also briefly be touched upon.

Keywords: arrhythmias; cardiomyocytes; clinical trials; electrotonic connections; stem cells.

Figure 1

Possible mechanisms of stem cell induced arrhythmias. (A) Depolarization of cardiomyocytes reduces the upstroke velocity and conduction velocity. (B) Clusters of stem cells can create an anatomical block and force the electrical pathway to find a different (and longer) route. (C) Stem cells can be spontaneously beating and may compete with the hosts own automaticity when engrafted. Stem cells may also be capable of inducing arrhythmias via triggered activity (D). (E) Increased sympathetic innervation induced by stem cells can give an unbalance in the sympathetic and parasympathetic equilibrium. (F) Paracrine factors released by stem cells may effect electrophysiology of cardiomyocytes.