Abstract
Lung transplantation offers a lifesaving therapy for patients with end-stage lung disease but its availability is presently limited by low organ utilization rates with donor lungs frequently excluded due to unsuitability at assessment. When transplantation does occur, recipients are then vulnerable to primary graft dysfunction (PGD), multitudinous short-term complications, and chronic lung allograft dysfunction. The decision whether to use donor lungs is made rapidly and subjectively with limited information and means many lungs that might have been suitable are lost to the transplant pathway. Compared to static cold storage (SCS), ex vivo lung perfusion (EVLP) offers clinicians unrivalled opportunity for rigorous objective assessment of donor lungs in conditions replicating normal physiology, thus allowing for better informed decision-making in suitability assessments. EVLP additionally offers a platform for the delivery of intravascular or intrabronchial therapies to metabolically active tissue aiming to treat existing lung injuries. In the future, EVLP may be employed to provide a pre-transplant environment optimized to prevent negative outcomes such as primary graft dysfunction (PGD) or rejection post-transplant.
Highlights
Even further potential for ex vivo lung perfusion (EVLP) lies in its scope as a platform for lung recovery via the administration of therapeutics to metabolically active and responsive cells, limiting or even reversing pre-existing lung injuries or those inherent to retrieval, fostering a lung environment best aligned with excellent outcome post-transplantation
EVLP has already been shown to be an effective tool for decellularization and with standard protocol EVLP with hepatitis C positive lungs, the wash out achieved a recellularization [46] and may provide a platform for assessment and safe use of bioengireduction in HCV RNA viral loads
Multipotent adult progenitor cells (MAPCs), an alternative cell therapy with shared characteristics with Mesenchymal stem cells (MSCs) have been preliminarily explored for use in EVLP, with one porcine EVLP model demonstrating reduced neutrophil infiltration and pro-inflammatory cytokines TNF-α, IL-1β and IFN-γ in lavage samples in the treatment group compared to controls [39]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Lungs falling outside ‘ideal’ criteria restrictions may not necessarily be contraindicated for donation and injury may be reversible or inconsequential Such organs are considered ‘marginal’ and expanded donor selection criteria have been implemented to encourage their use where appropriate. Even further potential for EVLP lies in its scope as a platform for lung recovery via the administration of therapeutics to metabolically active and responsive cells, limiting or even reversing pre-existing lung injuries or those inherent to retrieval, fostering a lung environment best aligned with excellent outcome post-transplantation. This review first outlines the development of EVLP, its role as a lung assessment tool and the current evidence surrounding its use It focuses on its great potential as a therapeutic platform in the future
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