Therapeutic potential of neural stem cell-derived exosomes and PRP in Parkinson's disease: A novel regenerative approach

Introduction: Parkinson's disease (PD) is a neurological ailment characterized by oxidative stress, neuroinflammation, and the progressive loss of dopaminergic neurons in the substantia nigra. The current treatments lack disease-modifying capabilities. The current study investigated the neuroprotective and regenerative efficacy of a combination of neural stem cell-derived exosomes (NMSC-EXO) and PRP in a rotenone-induced rat model of PD. Material and methods: Thirty male Wistar rats were randomly assigned to three equal groups (n = 10/group). Group I (negative Control): received subcutaneous (s.c) sunflower oil for 35 days followed by intravenous (i.v.) saline for 30 days. Group II (Rotenone model): administered 2 mg/kg/day rotenone s.c. for 35 days followed by i.v. saline for 30 days; Group III Rotenone + combination (Exosomes + PRP): received 2 mg/kg/day rotenone s.c. for 35 days, followed by biweekly i.v. injection of 109 NMSC-EXO in 250 μl PRP for 30 days. Evaluation starts 65 days from the beginning, evaluation included behavioural assessments (wire hanging, ladder climbing, open field), histological and immunohistochemical evaluation of substantia nigra (tyrosine hydroxylase [TH] and caspase 1), qRT-PCR gene expression (integrin [Itg] and [TH]), as well as oxidative stress markers (GSH and MDA). Results: The co-administration of NMSC-EXO and PRP significantly attenuated rotenone-induced motor deficits, thereby restoring locomotor activity, balance, and exploratory behavior. Dual therapy preserved dopaminergic neurons in the substantia nigra, downregulated the apoptotic marker caspase-1, and significantly decreased lipid peroxidation (MDA) while restoring reduced glutathione (GSH) levels. Furthermore, treatment led to significant upregulation of tyrosine hydroxylase and integrin expression relative to the rotenone model group. Conclusion: Combined NMSC-EXO and PRP therapy exerted strong neuroprotective, antioxidant, and anti-apoptotic effects against rotenone-induced neurotoxicity. This synergetic approach represents a novel, cell-free regenerative strategy for Parkinson's disease.