Extracellular Vesicles in Lung Transplantation: Biomarkers, Pathophysiological Players, and Therapeutic Weapons?

In the field of lung transplantation (LTx), the survival of lung transplant recipients (LTRs) is limited by events such as primary graft dysfunction (PGD), infections, and acute rejection (AR), which promote the development of chronic lung allograft dysfunction (CLAD). Extracellular vesicles (EVs), including exosomes and microvesicles, have emerged as key players in LTx because of their roles in immune regulation, inflammation, and antigen presentation. EVs carry immunologically active molecules such as MHC class I/II proteins, cytokines, and lung self-antigens (SAgs), suggesting their involvement in infections and both AR and CLAD. Recent studies indicate that EVs have diagnostic and prognostic potential. EVs expressing HLA-G and SAgs correlate with graft outcomes, while circulating EV-associated miRNAs are being evaluated as noninvasive biomarkers of rejection. In addition to their diagnostic potential, mesenchymal stem cell-derived EVs show promise in managing PGD by reducing inflammation, mitigating ischemia‒reperfusion injury, and enhancing lung repair. In conclusion, EVs contribute to pathogenesis, have potential as biomarkers, and hold promise as tools for improving LTx outcomes as therapeutic agents, yet further research is needed to validate their clinical application in the prediction and management of CLAD.