Stem Cell-Derived Exosomes with High Expression of PD-L1 as Nanotherapeutics in Rheumatoid Arthritis Model Mice.

Abstract

<h4>Purpose</h4>Previous studies have identified synovial T cells as key pathogenic drivers of rheumatoid arthritis (RA). To explore a novel therapeutic strategy targeting these cells, we aimed to develop mesenchymal stem cell-derived exosomes with enhanced PD-L1 expression (Exo-PD-L1) and evaluate their therapeutic potential in RA.<h4>Methods</h4>Mouse bone marrow mesenchymal stem cells (MSCs) were stimulated with interferon γ (IFN-γ) to upregulate programmed death ligand 1 (PD-L1) expression. Exo-PD-L1 was isolated and administered to collagen-induced arthritis (CIA) model mice. Therapeutic effects were assessed through T cell activity assays, in vivo biodistribution tracking, clinical symptom scoring, and histopathological analysis of extremities and major organs.<h4>Results</h4>Exo-PD-L1 significantly inhibited the activity of cultured T cells, was highly concentrated in the joints of RA mice, and significantly improved RA manifestations and histological abnormalities in the extremities of mice. No histological abnormalities were observed in the main organs of the mice.<h4>Conclusion</h4>Exo-PD-L1 can be homed to inflammatory lesions and have the potential to treat RA.