PD-L1-Expressing Extracellular Vesicles for the Treatment of Pneumonia.
Yi WuHeng WangAnning SongXiaoyu WangQingle MaChenlu YaoJialu XuHuaxing DaiChao WangTing LuFang XuPublished in: ACS biomaterials science & engineering (2023)
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.
Keyphrases
- lps induced
- acute respiratory distress syndrome
- inflammatory response
- extracorporeal membrane oxygenation
- signaling pathway
- mechanical ventilation
- respiratory failure
- poor prognosis
- high fat diet induced
- cardiovascular events
- stem cells
- pi k akt
- epithelial mesenchymal transition
- emergency department
- type diabetes
- wild type
- cell proliferation
- intensive care unit
- risk factors
- coronary artery disease
- binding protein
- metabolic syndrome
- cardiovascular disease
- long non coding rna
- newly diagnosed
- insulin resistance
- induced apoptosis
- skeletal muscle