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

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.

Mesenchymal stromal cell derived extracellular vesicles as a therapeutic tool: immune regulation, MSC priming, and applications to SLE

“…Wu et al. have shown that PD-L1 overexpressing MSC-EVs have enhanced therapeutic activity compared to native EVs in a model of LPS-induced pneumonia in mice ( 77 ). Other teams also used PD-L1 overexpressing MSC-EVs, showing an increased therapeutic activity in their in vitro and in vivo models.…”

“…Genetic modifications of MSC producing EVs can improve the immunomodulatory potential of MSC-EVs. A few studies already described above have targeted specific immunomodulatory proteins such as IDO ( 100 ), IL-10 ( 44 ), TSG-6 ( 52 ), TGF-β, PTX3, miR-let7-5p and miR-21-5p ( 25 ), CD73 ( 66 ), PD-L1 ( 77 – 79 ), in order to secrete more of these specific proteins and induce a better immunoregulatory activity of MSC-EVs. Genetic modifications can also target the expression of bioactive miRNAs.…”