Protective effects of exosomes-derived from human amniotic fluid stem cells intranasally administered in a unilaterally lesioned 6-OHDA mouse model

Parkinson’s disease (PD) is a progressively debilitating neurodegenerative disorder that leads to motor and cognitive dysfunction. To date, clinical treatment can only ameliorate symptoms, but cannot efficiently protect dopaminergic neurons. Several reports have demonstrated that human amniotic fluid stem cells (hAFSCs) provide protective effects on brain injury. Stem cells communicate with cells through secreted exosomes, the present study aimed to explore whether exosomes derived from hAFSCs-conditioned media may exert a protective effect in a mouse model of PD. The exosomes were characterized, and then labeled with PKH 26 (in order to visualize them fluorescently into the brain) and administered intranasally (i.n.) in a mouse model of PD, obtained by unilateral 6-OHDA injection into the striatum. We decided to use intranasal administration because it is one of the less invasive routes of administration and because through i.n. administration exosomes are able to cross the BBB. Behavioral tests (gait analyses, cylinder test, elevated body swing test and apomorphine) and tyrosine hydroxylase (TH) expression in the nigro-striatal structures were performed. We then analyzed the inflammatory pathway, through Iba1 immunofluorescence, Proteome Profiler Array and ELISA kits for IL-8 (GRO/KC), NFKB and so on. Notably, it was found that the exosomes relieved apomorphine-induced asymmetric rotation and improved behavioral performances in 6-OHDA mice, reduced substantia nigra dopaminergic neuron loss and inflammation. These results demonstrated that hAFSCs-exosomes can cross the BBB and can represent a potential approach for PD.