Stem cell therapy for myocardial infarction: are we missing time?

The success of stem cell therapy in myocardial infarction (MI) is modest, and for stem cell therapy to be clinically effective fine-tuning in regard to timing, dosing, and the route of administration is required. Experimental studies suggest the existence of a temporal window of opportunity bound by the acute inflammatory response on one hand and by scar formation on the other. In the meantime, microenvironmental factors must favor stem cell homing, survival, differentiation, and integration for stem cell therapy to be effective. Clinical data on the optimal timing of treatment are scarce. Experimental studies and clinical subgroup analyses can provide a clue and useful guidance for further research. In this review, the fundamental mechanisms as well as trial results important for the determination of the optimal timing of stem cell therapy following MI are summarized and discussed. We conclude that optimization of stem cell therapy requires further research on the fundamental mechanisms responsible for stem cell homing, survival, differentiation, and integration. Clinically, randomized trials with bone-marrow-derived stem cells should be conducted timing therapy at different points within the first month after MI, which seems to be the most promising period for this cell type.