Cell therapy for heart disease and arrhythmias: different cell different outcome

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The take-home message from a session on the electrophysiological aspects in stem cell therapy at the recent EHRA-Europace Congress (Madrid, Spain) is that more research is needed to resolve the issue of the risk of arrhythmias with the use of stem cells in myocardial repair.

In his talk Cell integration in myocardial repair: an ongoing debate, Massimiliano Gnecchi, Department of Cardiology, University of Pavia & IRCCS Policlinico San Matteo, Pavia, Italy, summarised the results of the most significant experimental works testing cell therapy to repair myocardial damage. He showed that besides myocardial regeneration, stem cells act mainly through paracrine mechanisms that protect ischaemic myocardium and ameliorate cardiac function. Then, Gnecchi focused on the three cell types that have already been tested in clinical trials and exposed their potential pro-arrhythmic roles: skeletal myoblasts, bone marrow-derived mononuclear cells, and mesenchymal stem cells. Skeletal myoblasts, a progenitor cell type meant to regenerate skeletal muscle, have shown potential hazard with occurrence of malignant arrhythmias in some patients. The main reason for their pro-arrhythmic effect is because they do not integrate electrically with the host cardiomyocyts; bone marrow-derived mononuclear cells may also have pro-arrhythmic properties, but so far no significant arrhythmias have been noted in clinical trials; and mesenchymal stem cells, the only real stem cell type tested thus far in humans, have convincing data, both in experimental and clinical settings, that that they have a potential antiarrhythmic action.

Pyotr Platonov, Department of Cardiology, Lund University Hospital, Lund, Sweden, outlined the perfect stem cell, in terms its electrophysiological properties, as being one that has a neutral effect, integrates and couples with surrounding viable host cardiomyocytes, and has ion channel electrical properties similar to host cardiomyocytes (automaticity, excitability, and replorisation). He concluded that from the electrophysiological perspective, there was no perfect stem cell. Embryonic cells possess the lowest arrhythmia risk but are associated with a teratogenic risk and ethical concerns. He put forward grafting or recruitment of cardiac stem cells and reprogramming of adult cells to pluripotent cells as possible solutions.

Joachim Ehrlich, Department of Cardiology, Clinical Electrophysiology, Goethe-University, Frankfurt, German, concluded the session by reviewing the evidence so far. He said. “We need more prospective data…we need more data to thoroughly control the problem [of the potential of arrhythmias with stem cells].”