Improving Long-Term Outcome in Allograft Transplantation: Role of Ionic Composition and Polyethylene Glycol
Résumé
Background. Ischemia reperfusion injury (IRI) is inherent to transplantation, and correlates with negative outcome. Limiting IRI requires new preservation. Fourth generation solutions are emerging, using new colloid based on polyethylene glycol (PEG) polymers and extracellular ionic composition. We evaluated their eventual benefits for optimal resistance to IRI and improved outcome. Methods. Using primary cell culture and a preclinical pig model of low-mismatch kidney allograft transplantation, not requiring immunosuppression, we compared the following solutions: UW (University of Wisconsin), high potassium with hydroxyethyl starch, gold standard in preservation; IGL-1 (Institute George Lopez-1), low potassium solution using PEG (35 kDa, 1 g/L); and SCOT (Solution de Conservation des Organes et Tissus), plasma-like ionic composition, containing PEG 20 kDa (30 g/L). Results. In vitro, SCOT-preserved cells had better viability and less necrosis. In vivo, SCOT-grafts had better function recovery, with limited histological injury compared with the other solutions. During the 3 months follow-up, we found low innate and adaptative immune response in SCOT organs, whereas other groups presented high rate of invasion and antigen presentation. SCOT-preserved kidneys showed low fibrosis, transforming growth factor-beta expression and apoptosis compared with the other groups. These differences impacted survival at 3 months, which was low in UW (20%) and IGL-1 (40%) groups, whereas it remained high for SCOT animals (80%, P < 0.05 to UW). Conclusions. In conclusion, plasma-like ionic composition and nontoxic molecule PEG provide high resistance against IRI and optimize graft outcome. Such solutions could be invaluable for the use of fragile organs, such as from extended criteria or deceased after cardiac death donors.