Effects of Mesenchymal Stem Cell-Derived Exosomes on Lung Inflammation in a Murine Aspiration Model.

Abstract

Aspiration pneumonia is a major cause of morbidity and mortality in adults with swallowing impairment. Exosomes from mesenchymal stromal cells (MSCs) present a potential therapeutic for aspiration pneumonia. This study aimed to assess the potential of MSC exosomes to mitigate lung inflammation in a murine aspiration model. Seventeen adult male rats were divided into three groups: Animals in the LPS-EXO group (n = 7) underwent intratracheal instillation of 2.5 mg/kg lipopolysaccharide (LPS) aspirate and 40 μL of MSC exosome therapeutic intravenously. The LPS-only group (n = 7) underwent LPS aspiration alone without exosome therapy. Three rats underwent instillation of air as sham controls. All animals were euthanized 6 h post instillation. Histopathologic lung injury severity was determined and gene expression of pro and anti-inflammatory cytokines was evaluated using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). The mean composite histologic lung injury score was 8.3 (±1.1) for the LPS-only group, 7.13 (±3.2) for the LPS-EXO treatment group, and 3.3 (±1.1) for the sham control group. One-way ANOVA showed a significant group effect (p = 0.02), and trend analysis revealed a significant linear improvement across groups (p = 0.006; η² = 0.43). qRT-PCR showed significantly lower Tnf expression in the LPS-EXO group versus the LPS-only group (p < 0.05). No other significant differences were found between the LPS-EXO and LPS-only groups on qRT-PCR. Results of this preliminary investigation suggest that intravenous delivery of MSC exosomes reduces expression levels of proinflammatory cytokine Tnf and attenuates histopathological markers of lung injury in a murine model of aspiration-induced lung damage. NA.