Controlling the fate of regenerative cells with engineered platelet-derived extracellular vesicles

Extracellular vesicles (EVs) have emerged as cell-free nanotherapeutic agents for the potential treatment

of multiple diseases and for tissue engineering and regenerative medicine strategies. Nevertheless, the

field has typically relied on EVs derived from stem cells, the production of which in high quantities and

high reproducibility is still under debate. Platelet-derived EVs were produced by a freeze–thaw method of

platelet concentrates, a highly available clinical waste material. The aim of this study was to produce and

thoroughly characterize platelet-derived EVs and understand their effects in adipose-tissue derived stem

cells (hASCs), endothelial cells (HUVECs) and macrophages. Two different EV populations were obtained

after differential centrifugation, namely small EVs (sEVs) and medium EVs (mEVs), which showed different

size distributions and unique proteomic signatures. EV interaction with hASCs resulted in the modulation

of the gene expression of markers related to their commitment toward different lineages. Moreover,

mEVs showed higher angiogenic potential than sEVs, in a tube formation assay with HUVECs. Also, the

EVs were able to modulate macrophage polarization. Altogether, these results suggest that plateletderived

EVs are promising candidates to be used as biochemical signals or therapeutic tools in tissue

engineering and regenerative medicine approaches.