Canine Stem Cell-derived Exosomes for Lung Inflammation: Efficacy of Intratracheal Versus Intravenous Administration in an Acute Lung Injury Mouse Model

Background/Aim: Acute lung injury (ALI) is an important pathological process in acute respiratory distress syndrome; however, feasible and effective treatment strategies for ALI are limited. Recent studies have suggested that stem cell-derived exosomes can ameliorate ALI; however, there remains no consensus on the protocols used, including the route of administration. This study aimed to identify the appropriate route of administration of canine stem cell-derived exosomes (cSC-Exos) in ALI. Lipopolysaccharides were used to induce ALI. Materials and Methods: Mice with ALI were treated with cSC-Exos by intratracheal instillation or intravenous injection. The efficacy of the route of administration was confirmed by determining the total cell count in the bronchoalveolar lavage fluid and histopathological changes. The treatment mechanism was confirmed by measuring cytokine levels and immune cell changes in M2 macrophages (CD206+ cells) and regulatory cells (FOXP+ cells). Results: When cSC-Exos were injected, inflammation was alleviated, pro-inflammatory cytokine levels were reduced, and FOXP3+ and CD206+ cells were activated. Following intratracheal instillation, an enhanced inflammation- relieving response was observed. Conclusion: This study compared the effects of stem cell-derived exosomes on alleviating lung inflammation according to injection routes in an ALI mouse model. It was confirmed that direct injection of exosomes into the airway had a greater ability to alleviate lung inflammation than intravenous injection by polarizing M2 macrophages and increasing regulatory T cells.