Abstract: Objective To investigate the therapeutic effects of murine pancreatic cancer cell line Pan02l-derived exosomes(Exos) on Parkinson's disease (PD) in a mouse model. Methods Pan02 cell-derived exosomes were extracted by commercially available kit and then characterized by transmission electron microscape(TEM), nanoparticle tracking analysis and Western blot. In vitro, the protective effect of exosomes on a mouse model of 1-methyl-4-phenylpyridinium (MPP⁺)-induced MN9D dopaminergic neuron injury was detected by CCK-8 assay. A C57BL/6J mice of acute 1-methyl-4-phenyl-1,2, 3, 6-tetrahydropyridine (MPTP)-induced PD was established. The mice were divided into a wild-type (WT) control group, a PD model group, and low, medium, and high-dose exosome groups (Exo-L, Exo-M, Exo-H). Exosomes were administered via multiple tail vein injections. Motor function and neurobehavioral changes were assessed using the balance beam test, pole test, rotarod test, open field test and Y-maze test. Damage to dopaminergic neurons in the substantia nigra and striatum was evaluated by immunofluorescence microscopy. A tumor-bearing mouse model was also established for a preliminary safety evaluation. Results Exosomes markedly reversed the MPP⁺-induced decrease in MN9D cell viability (P＜0.001). Compared with the PD model group, the Exo-L group showed a substantial reduction in beam crossing time (P＜0.001) and pole descent time (P＜0.05). The Exo-M group exhibited a significant decrease in total distance moved in the open field test (P＜0.05). No notable differences were observed in anxiety and cognition-related behavioral parameters among all groups. Exosomes dramatically mitigated MPTP-induced loss of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (Exo-L group, P＜0.05; Exo-H group, P＜0.01) and reduction of TH-positive fiber density in the striatum (Exo-L and Exo-M groups, P＜0.05). Safety evaluation confirmed that exosomes did not promote tumor growth in tumor-bearing mice. Conclusions Pan02 cell-derived exosomes effectively alleviate MPP⁺/MPTP-induced dopaminergic neuron injury, ameliorate motor dysfunction in PD mouse models, and exhibit no tumor-promoting risk, demonstrating favorable neuro-protective effects and safety.

Key words: Parkinson's disease, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), Pan02 cell, exosome