893: EXOSOMES FROM MESENCHYMAL STEM CELLS ALLEVIATE ASPIRATION-INDUCED LUNG INJURY IN MICE

Abstract

Introduction: With acidic fluid, the particulate component of the aspirate and pepsin, and bacteria from the oral cavity, gastric or oropharyngeal contents aspiration readily induces lung injury. Effective therapy remains lacking to date. The exaggerated inflammatory response has been identified as one crucial mechanism that mediates the development of lung injury in this regard. Exosomes from mesenchymal stem cells (MSCs) possess a potent anti-inflammation capacity. Based on these data, we thus conjectured that exosomes from MSCs may mitigate aspiration-induced acute lung injury. To elucidate further on this issue, we thus conducted this murine study. Methods: Adult male C57BL/6 mice were randomly allocated to the Sham group (oropharyngeal aspiration of normal saline), the AP group (oropharyngeal aspiration of mimic gastric content) or the AP-EXO group (AP plus exosomes) (n=6 in each group). The mimic gastric content consisted an acidic (pH 1.6) mixture of 12mg/mL ThickenUp®, 25μL pepsin (2mg/mL) and 20μL lipopolysaccharide (2.5mg/mL). In the AP-EXO group, mice received exosomes (1x10^8 particles/mouse, intratracheal, isolated from human placenta-derived MSCs) at 2 and 24 hours after aspiration. All mice were closely monitored for 48 hours, and each group’s lung injury level was measured. Results: Aspiration induces significant alterations in respiratory function, as our data revealed significantly higher airway resistance and lower forced expiratory volume in 0.1 seconds (FEV0.1) and dynamic compliance in mice of the AP group compared with the Sham group (all p< 0.001). Aspiration also induces significant airway inflammation, lung tissue edema and lung injury, as our data revealed significantly higher cell numbers in bronchoalveolar fluid, wet/dry weight ratio of lung tissue and lung injury score in mice of the AP group compared with the Sham group (all p< 0.001). These adverse effects of aspiration were mitigated by exosomes from MSCs, as our data demonstrated significantly lower airway resistance and, in contrast, higher FEV0.1 and dynamic compliance. Also, cell number in BALF, wet/dry weight ratio of lung tissues and lung injury score decreased in mice of the AP-EXO group compared with the AP group (all p< 0.001). Conclusions: Exosomes from MSCs mitigate aspiration-induced acute lung injury in mice.