Mesenchymal Stem Cell-Derived Extracellular Vesicles with High PD-L1 Expression for Autoimmune Diseases Treatment.

Abstract

Autoimmune diseases are the third most common disease influencing the quality of life of many patients. Here, a programmed cell death-ligand 1 + (PD-L1) mesenchymal stem cell (MSC) derived extracellular vesicles (MSC-sEVs-PD-L1) using lentivirus-mediated gene transfection technology is developed for reconfiguration of the local immune microenvironment of affected tissue in autoimmune diseases. MSC-sEVs-PD-L1 exhibits an impressive ability to regulate various activated immune cells to an immunosuppressed state in vitro. More importantly, in dextran sulfate sodium-induced ulcerative colitis (UC) and imiquimod-induced psoriasis mouse models, a significantly high accumulation of MSC-sEVs-PD-L1 is observed in the inflamed tissues compared to the PD-L1+ MSCs. Therapeutic efficiency in both UC and psoriasis mouse disease models is demonstrated using MSC-sEVs-PD-L1 to reshape the inflammatory ecosystem in the local immune context. A technology is developed using MSC-sEVs-PD-L1 as a natural delivery platform for autoimmune diseases treatment with high clinical potential.