Abstract: Objective: To investigate the effects of human dental pulp stem cell-derived extracellular vesicles (hDPSC-EVs) on Schwann cells' (SCs) functions in LPS-induced inflammatory microenvironment in vitro. Methods: hDPSCs and hDPSC-EVs were isolated and identified. hDPSC-EVs' effects on SCs proliferation and migration were assessed by CCK-8 and wound healing assays in normal conditions. SCs were treated with 1.0 μg/mL LPS for 72 h to establish an inflammatory model. Groups included Control, LPS, LPS + hDPSC-EVs, LPS + hDPSC-CM, and LPS + GW4869-CM. Meanwhile, the expression level of inflammatory factors (IL-6, TNF-α, and IL-10) and neurotrophic factors (BDNF and NGF) were examined by RT-qPCR and ELISA. Results: Under normal condition, hDPSC-EVs substantially improved SCs' proliferation (P<0.05) and migration (P<0.001). In LPS-induced inflammatory model, hDPSC-EVs markedly decreased the expression level of IL-6 and TNF-α while upregulated secretion of IL-10, BDNF, and NGF. These modulations were attenuated by the EVs inhibitor GW4869. Conclusion: hDPSC-EVs can modulate the expression of inflammation-related factors and promote the expression of neurotrophic factors in SCs under an inflammatory microenvironment.

Key words: human dental pulp stem cells, extracellular vesicles, inflammatory microenvironment, Schwann cells, facial nerve injury