Small Extracellular Vesicles Derived From Mesenchymal Stem Cells Exert Neuroprotective Effect Against a Model of Dopamine Dysfunction by Inhibiting Caspase-8/Caspase-3-Mediated Apoptosis.

BACKGROUND

The precise pathological mechanisms driving Parkinson's disease (PD) progression remain incompletely understood, and there are currently no therapies that can modify the course of the disease. While mesenchymal stem cells (MSCs) hold therapeutic potential for various conditions, their clinical utility is constrained by challenges in sourcing and limited availability.

METHODS

This study investigated a novel therapeutic approach using trophoblast-derived mesenchymal-like stem cells (T-MSCs), which can be stably generated from commercially available embryonic stem cells, and the small extracellular vesicles (T-MSCs-sEVs) that they secrete. We explored the therapeutic effects against PD by inhibiting Caspase-8/Caspase-3-mediated apoptosis both in vitro and in vivo using experimental assays (e.g., flow cytometry (FCM) analysis, western blotting, and immunofluorescence staining).

RESULTS

The selected cytokine Clusterin was validated via G-Series Mouse Cytokine Antibody Array 4000 (GSM-CAA-4000) using ELISA kits, which revealed its involvement in apoptosis during the PD process. Moreover, T-MSCs and T-MSCs-sEVs could alleviate dopaminergic (DA) neuron damage in vitro and in vivo by inhibiting the Caspase-8/Caspase-3-mediated apoptotic pathway.

CONCLUSIONS

The results suggest that T-MSCs-sEVs represent a promising biological candidate for future therapeutic strategies aimed at treating PD.