STIM-ulation for the big trial

Ischaemic heart disease is one of the leading causes of morbidity and mortality in the industrialised world. Although pharmacological and interventional strategies for revascularisation have improved the outcome of ischaemic heart disease, the possibility of reversing progressive ventricular remodeling remains a major unresolved clinical problem. Furthermore, after myocardial infarction the endogenous regenerative capacity of the damaged organ is not sufficient to restore ventricular mass and function. Ventricular dilation and relative wall thinning enhance the mechanical load on the surviving cardiomyocytes, triggering a cascade of events that lead to severe myocardial dysfunction and, ultimately, terminal failure. Novel therapeutic approaches are therefore needed, pointing to exogenous and endogenous stem/progenitor cells as a potential form of treatment for this devastating disease [1‐7]. Studies in animals have suggested that adult bone marrow stem cells transdifferentiate, possessing the unique capacity to create cardiomyocytes and coronary vessels, critical for the regeneration of the infarcted myocardium. These experimental findings have prompted numerous clinical trials, which collectively have shown relatively positive results. However, rapid implementation of bone marrow mononuclear cells (BM-MNC) in patients affected by acute myocardial infarction has stimulated heated discussion in the scientific community, with strong supporters and equally charged opponents of this type of cell therapy for the human disease. Numerous questions had to be addressed in clinical trials: method of administration, timing of delivery, cell type, number of cells and, most importantly, the safety and feasibility of this approach. Many protocols for stem cell treatment have been used, including intravenous, transarterial, intracoronary and intramyocardial (including transepicardial and transendocardial) administration modalities. The least invasive route of delivery is intravenous infusion, which has the disadvantage that the majority of cells may be trapped in the pulmon