Treatment of Parkinson's disease model with human umbilical cord mesenchymal stem cell-derived exosomes loaded with BDNF.

AIMS: Parkinson's disease (PD) is a common neurodegenerative disease that has received widespread attention; however, current clinical treatments can only relieve its symptoms, and do not effectively protect dopaminergic neurons. The purpose of the present study was to investigate the therapeutic effects of human umbilical cord mesenchymal stem cell-derived exosomes loaded with brain-derived neurotrophic factor (BDNF-EXO) on PD models and to explore the underlying mechanisms of these effects.

MAIN

METHODS

6-Hydroxydopamine was used to establish in vivo and in vitro PD models. Western blotting, flow cytometry, and immunofluorescence were used to detect the effects of BDNF-EXO on apoptosis and ferroptosis in SH-SY5Y cells. The in vivo biological distribution of BDNF-EXO was detected using a small animal imaging system, and dopaminergic neuron improvements in brain tissue were detected using western blotting, immunofluorescence, immunohistochemistry, and Nissl and Prussian blue staining.

KEY FINDINGS: BDNF-EXO effectively suppressed 6-hydroxydopamine-induced apoptosis and ferroptosis in SH-SY5Y cells. Following intravenous administration, BDNF-EXO crossed the blood-brain barrier to reach afflicted brain regions in mice, leading to a notable enhancement in neuronal survival. Furthermore, BDNF-EXO modulated microtubule-associated protein 2 and phosphorylated tau expression, thereby promoting neuronal cytoskeletal stability. Additionally, BDNF-EXO bolstered cellular antioxidant defense mechanisms through the activation of the nuclear factor erythroid 2-related factor 2 signaling pathway, thereby conferring neuroprotection against damage.

SIGNIFICANCE: The novel drug delivery system, BDNF-EXO, had substantial therapeutic effects in both in vivo and in vitro PD models, and may represent a new treatment strategy for PD.