Updated project metadata. The use of cardiac progenitor cell (CPC)-derived small extracellular vesicles (sEVs) has shown potential to stimulate cardiac repair. sEVs are released by cells and play a role in intercellular communication through transfer of their bioactive content. Increasing evidence indicates that sEVs present a heterogeneous population of vesicles. In the context of cardiac regeneration, studying sEV heterogeneity could provide new insights into mechanisms underlying sEV-mediated cardiac repair properties and help to improve the therapeutic application of CPC-derived sEVs. Here we used size-exclusion chromatography to isolate and fractionate EV subpopulations dervied from CPCs. We then applied a bottom-up proteomic approach to characterize the contents of individual EV subpopulations.