Pericyte-derived extracellular vesicles-mimetic nanovesicles improves peripheral nerve regeneration in mouse models of sciatic nerve transection

Pericyte-derived extracellular vesicle-mimetic nanovesicles (PC-NVs) play an important role in the improvement of erectile function after cavernous nerve injury. However, the impact of PC-NVs on the peripheral nervous system (PNS), such as the sciatic nerve, is unclear. In this study, PC-NVs were isolated from mouse cavernous pericytes (MCPs). A sciatic nerve transection (SNT) model was established using 8-week-old C57BL/6J mice. The sciatic nerve was harvested 5 and 14 days for immunofluorescence and western blot studies. Function studies were evaluated by performing the rotarod test and walking track analysis. The results demonstrated that PC-NVs could stimulate endothelial cells, increase neuronal cell content, and increase macrophage and Schwann cell presence at the proximal stump rather than the distal stump in the SNT model, thereby improving angiogenesis and nerve regeneration in the early stage of sciatic nerve regeneration. In addition, PC-NVs also increased the expression of neurotrophic factors (brain-derived nerve growth factor, neurotrophin-3 and nerve growth factor) and the activity of the cell survival signaling pathway (PI3K/Akt signaling), and reduced the activity of the JNK signaling pathway. Additionally, after 8 weeks of local application of PC-NVs in SNT model mice, their motor and sensory functions were significantly improved, as assessed by performing the rotarod test and walking track analysis. In conclusion, the present study showed that the significant improvement of neurovascular regeneration in mice following treatment with PC-NVs may provide a favorable strategy for promoting motor and sensory regeneration and functional recovery of the PNS.