Exosomes produced from stem and progenitor cells, including the ones isolated from cultured adult cardiac progenitor cells (CPCs), which have been claimed to reside in the human heart and contribute to myocardial regeneration, have shown proangiogenic effects.24, 25 However, the in vivo abundance and physiological relevance of CPCs are currently intensively questioned,26, 27 thus discouraging the speculation that exosomes released in vivo by CPCs play a major role in heart homeostasis. Stem and progenitor cells still represent hope for vascular regeneration. In a seminal paper, Sahoo et al.28 showed that bone marrow mononuclear cell (MNC)-derived CD34-positive cells promote therapeutic angiogenesis in vitro and in vivo via paracrine actions that can be recapitulated by their exosomes, but not by exosomes from MNCs. Later studies have expanded on this to recognize that proangiogenic exosomes are released in culture by the different types of progenitor cells so far trialled in patients with heart ischemia.13 These findings open new exciting therapeutic avenues but do not address the contribution of endogenous exosomes to cardiovascular physiopathology. Additionally, not all exosomes stimulate angiogenesis. As an example, exosomes from diabetic cardiomyocytes reportedly inhibited endothelial cell (EC) survival and angiogenesis by the transfer of miRNA-320.29