Mesenchymal stem cell therapy against ischemia-reperfusion injury in lung transplantation.

Ischemia-reperfusion injury (IRI) remains a major challenge in lung transplantation, contributing to early graft dysfunction and negatively affecting long-term outcomes. This review highlights recent advances in the use of mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) as emerging therapeutic approaches to reduce IRI and improve graft viability. MSCs exert beneficial effects through paracrine mechanisms, including the release of EVs that carry bioactive molecules such as microRNAs, cytokines, and growth factors. These vesicles play a critical role in modulating the immune response, reducing inflammation, and promoting tissue repair. In preclinical models, MSCs and EVs have been shown to limit neutrophilic infiltration, downregulate pro-inflammatory mediators, and enhance alveolar fluid clearance. Furthermore, the use of ex vivo lung perfusion (EVLP) has emerged as a promising platform for the controlled administration of MSCs and EVs, allowing for targeted intervention prior to implantation. Accumulating preclinical data support the potential of MSC- and EV-based therapies to mitigate IRI and improve graft function. Clinical translation will depend on refining delivery strategies, determining optimal dosing, and ensuring reproducibility - particularly when integrated with EVLP protocols.