Effectiveness of mesenchymal stem cell-derived extracellular vesicles therapy for Parkinson's disease: A systematic review of preclinical studies.

BACKGROUND: Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) can traverse the blood-brain barrier due to their small size. This characteristic makes them a research hotspot for the treatment of Parkinson's disease (PD) and is expected to be a potentially revolutionary strategy for treating PD. Despite this, no summary of clinical trial results has been reported. AIM: To assess the efficacy and durability of MSC-EVs in treating PD. METHODS: Systematic searches were conducted in four electronic databases until June 2024 to collect studies on the use of MSC-EVs for this purpose. Thirteen relevant randomized controlled trials, encompassing 16 experiments, were selected for inclusion. RESULTS: Behavioral assessments, including the rotarod and apomorphine turning behavior tests, indicated improvements in motor coordination (P < 0.00001); the Pole test and the Wire-hang test showed enhanced limb motor agility and synchronization (P = 0.003 and P < 0.00001, respectively). Histopathologically, there was a reduction in inflammatory markers such as tumor necrosis factor-α and interleukin-6 (P = 0.03 and P = 0.01, respectively) and an increase in tyrosine hydroxylase-positive cells in the lesion areas (P < 0.00001). CONCLUSION: MSC-EV therapy for PD is a gradual process, with significant improvements observable more than 2 weeks after administration and lasting at least 8 weeks. This study is the first to demonstrate the efficacy and durability of MSC-EV treatment in PD.