Current Status and Future Perspectives on Machine Perfusion: A Treatment Platform to Restore and Regenerate Injured Lungs Using Cell and Cytokine Adsorption Therapy

Abstract

Since its advent in the 1990′s, ex vivo lung perfusion (EVLP) has been studied and implemented as a tool to evaluate the quality of a donor organ prior to transplantation. It provides an invaluable window of opportunity for therapeutic intervention to render marginal lungs viable for transplantation. This ultimately aligns with the need of the lung transplant field to increase the number of available donor organs given critical shortages. As transplantation is the only option for patients with end-stage lung disease, advancements in technology are needed to decrease wait-list time and mortality. This review summarizes the results from the application of EVLP as a therapeutic intervention and focuses on the use of the platform with regard to cell therapies, cell product therapies, and cytokine filtration among other technologies. This review will summarize both the clinical and translational science being conducted in these aspects and will highlight the opportunities for EVLP to be developed as a powerful tool to increase the donor lung supply.

Taking a Deep Breath: an Examination of Current Controversies in Surgical Procedures in Lung Transplantation

“…Given the severe shortage of donor organs, the application of ex vivo lung perfusion (EVLP) presents as a method for evaluating marginal lungs [ 60 ••]. Its development may increase the transplanted donor pool and it holds potential as a timepoint at which therapeutic approaches could be applied to recover an injured lung [ 61 ]. The method was originally designed to re-evaluate DCD lungs ex vivo in an extracorporeal membrane oxygenation circuit to allow for the ventilation, oxygenation, and perfusion of an explanted lung [ 62 ].…”

Is there life on the airway tree? A pilot study of bronchial cell vitality and tissue morphology in the ex vivo lung perfusion (EVLP) era of lung transplantation

“…Indeed, in other transplant settings, ex vivo machine perfusion has already proved to represent a reliable technique to provide specific treatments aiming to improve graft functionality 38–40 . In the EVLP setting, this approach still needs to be thoroughly explored, but we believe that our data could represent a significant starting point 22,25–27 …”

“…Indeed, EVLP is a relatively recent procedure that has proved to (1) increase lung parenchyma recruitment, (2) reduce lung edema incidence and severity and improve graft gas exchange performance, thanks to the hyperoncotic solution perfusion, and (3) allow to implement specific treatments (e.g., antibiotics), ultimately increasing the donor graft pool 10,15,18–20,22–27 . Clinical trial results further supported its adoption by showing equal outcomes of EVLP‐treated grafts compared with the conventional approach 14,28–33 .…”

“…This evidence is particularly significant, as increasing research protocols are exploring the opportunity to provide therapeutical support to the graft during EVLP (e.g., gene and antibiotic therapy), but these approaches require prolonged procedure extent. 22 , 25 , 26 , 27 Indeed, in other transplant settings, ex vivo machine perfusion has already proved to represent a reliable technique to provide specific treatments aiming to improve graft functionality. 38 , 39 , 40 In the EVLP setting, this approach still needs to be thoroughly explored, but we believe that our data could represent a significant starting point.…”

Novel approaches for long-term lung transplant survival

“…Most preclinical studies of MSC treatment for lung IRI use intravenous or intraperitoneal infusion to deliver the cells, however, studies in lung transplantation have the unique opportunity to use EVLP for cell delivery. Combining MSC treatment with EVLP may enable the targeting of IRI before it occurs and reconditioning of lungs without the theoretical risks of microvascular embolism from high dose intravenous infusion of MSCs [reviewed in ( 141 ) and ( 142 )].…”