Protective effect of extracellular vesicles released from the neural stem cells on 6-hydroxydopamine induced neurotoxicity

Abstract

Neural stem cells (NSCs) are potential therapeutic resources for Parkinsons disease (PD) because they promote recovery of neuronal damage. NSC-secreted extracellular vesicles (EVs) are key mediators of positive paracrine effects. Direct evidence for neuronal protective effects of EVs is essential for developing new PD therapeutics. In this study, we observed the protective effects of NSC-derived EVs during neurotoxin 6-hydroxydopamine (6-OHDA)-induced degeneration of SH-SY5Y dopaminergic cells. To trace EV movement, a lentivirus containing Palm tandem dimer tdTomato (Palm-td) was transduced into F3 NSCs. EVs isolated from Palm-td–infected F3 cells showed high tdTomato fluorescence intensity. We found that pre-treatment with EVs dramatically prevented 6-OHDA-induced toxicity by reducing intracellular reactive oxygen species (ROS), percentage of apoptotic cells, and caspase-3/7 activity. These results indicate that NSC-derived EVs have neuroprotective effects against 6-OHDA-induced cell damage, possibly through anti-oxidant and anti-apoptotic action. The findings may provide further insights into potential therapeutic strategies using NSC-derived EVs for neuronal protection against oxidative stress.