Platelet concentrate-derived extracellular vesicles promote adult hippocampal neurogenesis

Abstract Emerging evidence suggests that platelet concentrate (PC) derivatives harbor neuroregenerative potential. Here, we evaluated the neurogenic effects of PC-derived human platelet lysate (HPPL) and extracellular vesicles (pEVs) on neural precursor cells using both an ex vivo neurosphere assay and an in vivo intranasal delivery model in adult mice. pEVs selectively enhanced the proliferation of dentate gyrus (DG)-derived neurospheres, and this region-specific effect persisted even without exogenous growth factors. In line with these findings, short-term intranasal administration of pEVs significantly increased cell proliferation in the DG. Long-term (28-day) pEVs treatment further elevated the proportion of newborn mature neurons in the DG, whereas HPPL primarily increased both proliferation and the number of immature neurons. Proteomic profiling of DG tissue after pEV treatment revealed 111 differentially expressed proteins, enriched in pathways related to oxidative phosphorylation, myelination, Notch4 signaling, and MHC class I processing. These findings identify allogeneic PC-derived EVs as potent, cell-free agents capable of promoting adult hippocampal neurogenesis and brain repair through metabolic and immunoregulatory mechanisms. KEY POINTS Platelet concentrate-derived extracellular vesicles (pEVs) enhance proliferation of adult neural progenitors in the dentate gyrus (DG), and activate myelination and immune metabolic pathways linked to neuronal integration. pEVs represent a minimally invasive, neuroregenerative biotherapy for brain repair.