Mapping the miRNA landscape of primitive macrophage extracellular vesicles highlights their pro-vasculogenic effects in engineered human cardiac tissue

However, the profile of their extracellular vesicles (EVs) in cardiac signalling and regulation remains uncharted. Here, we employ differentiation of human pluripotent stem cell (hPSC)-derived primitive macrophages (Mac) for isolation of their secreted EVs and in-depth characterization of EV-miRNA cargo.

Primitive macrophages secreted nanoscale EVs that expressed canonical EV markers, and miRNA sequencing highlighted a diverse and unique profile of miRNAs when compared to EVs sourced from other principal cardiac cell lineages and published data from monocyte-derived cells. In particular, we noted the abundance and enrichment of vascular-modulatory let-7 miRNAs and miR-126-3p. Functional screening of Mac-EVs in a 3D model of in vitro cardiac vasculogenesis confirmed enhanced early endothelial cell organization and branching.