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

Adv Mater. 2022 Jan;34(1):e2106265. doi: 10.1002/adma.202106265. Epub 2021 Oct 23.

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.

Keywords: PD-L1; autoimmune disease; extracellular vesicle; targeting.

MeSH terms

  • Animals
  • Autoimmune Diseases* / metabolism
  • Autoimmune Diseases* / therapy
  • B7-H1 Antigen / genetics
  • Ecosystem
  • Extracellular Vesicles* / metabolism
  • Humans
  • Mesenchymal Stem Cells* / metabolism
  • Mice
  • Quality of Life

Substances

  • B7-H1 Antigen