PD-L1-Expressing Extracellular Vesicles for the Treatment of Pneumonia

ACS Biomater Sci Eng. 2023 Nov 13;9(11):6464-6471. doi: 10.1021/acsbiomaterials.3c01173. Epub 2023 Oct 16.

Abstract

Acute respiratory distress syndrome (ARDS) is a severe lung condition with a high mortality rate and a lack of effective drug therapy. In this work, we developed mesenchymal stem cell (MSC)-derived extracellular vesicles with high PD-L1 expression (MSC-EVs-PD-L1) for treating lipopolysaccharide (LPS)-induced pneumonia by intratracheal administration. We found an upregulation of PD-1 expression in the inflammatory region of murine lungs; hence, MSC-EVs-PD-L1 exerted immunosuppressive effects via the PD-1/PD-L1 signaling pathway. Furthermore, we treated LPS-induced pneumonia mice by intratracheal administration, which enabled heavy drug accumulation in the lungs of mice and better therapeutic efficacy compared to systemic administration. Our results suggest that MSC-EVs-PD-L1 has the potential to provide a universal platform technology for the immunotherapy of pneumonia.

Keywords: acute respiratory distress syndrome; extracellular vesicles; immunotherapy; lipopolysaccharide-induced pneumonia; mesenchymal stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • Extracellular Vesicles* / metabolism
  • Lipopolysaccharides / metabolism
  • Mice
  • Pneumonia* / metabolism
  • Pneumonia* / therapy
  • Programmed Cell Death 1 Receptor / metabolism

Substances

  • B7-H1 Antigen
  • Lipopolysaccharides
  • Programmed Cell Death 1 Receptor