Dr Philippe Menasché is currently cardiac surgeon at the Hôpital Européen Georges Pompidou, Professor of Thoracic and Cardiovascular Surgery at the University of Paris Descartes, and Co-director of an INSERM (National Institute of Health and Medical Research) team devoted to cell therapy of cardiovascular diseases. The group has a long-standing interest in stem cells for the treatment of heart failure and has therefore developed small and large animal (including nonhuman primate) models of myocardial infarction and dilated cardiomyopathy. While the initial research has focused, both experimentally and clinically, on the transplantation of skeletal myoblasts, it has now moved towards the combination of cardiac progenitors derived from human embryonic stem cells (ESC) with a tissue engineering-based construct. The first-in-man trial testing this cell-loaded patch and primarily focused on feasibility and safety is now completed. In parallel, mechanistic studies of these cardiac progenitor cells have unravelled the predominant role of paracrine signalling and its mediation by cell-secreted extracellular vesicles. Consequently, the group is now shifting its research towards a-cellular cell therapy based on the exclusive use of these extracellular vesicles with the objective of a streamlined clinical translation.