Acute lung injury (ALI) is a severe clinical condition with high morbidity and mortality that usually results in the development of multiple organ dysfunction. The complex pathophysiology of ALI seems to provide a wide range of targets that offer numerous therapeutic options. However, despite extensive studies of ALI pathophysiology and treatment, no effective pharmacotherapy is available. Increasing evidence from both preclinical and clinical studies supports the preventive and therapeutic effects of mesenchymal stem cells (MSCs) for treating ALI. As cell-based therapy poses the risk of occlusion in microvasculature or unregulated growth, MSC-derived extracellular vesicles (MSC-EVs) have been extensively studied as a new therapeutic strategy for non-cell based therapy. It is widely accepted that the therapeutic properties of MSCs are derived from soluble factors with paracrine or endocrine effects, and EVs are among the most important paracrine or endocrine vehicles that can deliver various soluble factors with a similar phenotype as the parent cell. Therapeutic effects of MSCs have been reported for various delivery approaches, diverse doses, multiple origins, and different times of administration, and MSC-EVs treatment may include but is not limited to these choices. The mechanisms by which MSCs and MSC-EVs may contribute to ALI treatment remain elusive and need further exploration. This review provides an overview of preclinical studies that support the application of MSC-EVs for treating ALI, and it discusses emerging opportunities and their associated challenges.
Keywords: Acute lung injury; Animal model; Cell-free therapy; Extracellular vesicles; Intratracheal delivery; Mesenchymal stem cells; Pathophysiology.