Inhalation of Mesenchymal Stem Cell- Derived Small Extracellular Vesicles as a Possible Approach to Ameliorating Acute Lung Injury Caused by Cytokine Storm

Lung is one of the vital organs that get severely affected by cytokine storm and sepsis, leading to the development of acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Mesenchymal stem cell- derived small extracellular vesicles (MSC- derived sEVs) are one of the therapeutic approaches for ARDS/ ALI caused by sepsis. Apart from sEVs’ ability to carry medication, MSC- derived sEVs also possess anti- inflammatory, tissue repair, and regeneration properties. Targeted drug delivery has been a crucial area of concern in the medical field, specifically for treating lung diseases. To treat lung diseases locally, inhalation of drug products has been developed. Drug delivery by inhalation has emerged as an effective method for local administration of therapeutic agents, with numerous benefits including better efficacy at lower doses and decreased toxicity. Additionally, inhalation administration is a viable option for the systemic distribution of medications due to the lungs' considerable absorption surface and their ability to bypass initial metabolism. Therefore, our hypothesis proposes the inhalation of MSC- derived sEVs as a potential strategy for alleviating acute lung injury induced by sepsis-related cytokine storm. Following the isolation and characterization of these MSC- derived sEVs, they will be administered to an animal model of sepsis via a nebulizer, either in their pure form or loaded with drugs. Several approaches will be employed to evaluate lung functionality, including histological analysis and the measurement of inflammatory and regulatory cytokine levels to assess changes in both the humoral and cellular immune systems