Polyethylene Glycol 35 as a perfusate additive for mitochondrial and glycocalyx protection in HOPE liver preservation

Organ transplantation is a multifactorial process in which proper graft preservation is a mandatory step for the success of the transplantation. Hypothermic preservation of abdominal organs is mostly based on the use of several commercial solutions, including UW, Celsior, HTK and IGL-1. The presence of the oncotic agents HES (in UW) and PEG35 (in IGL-1) characterize both solution compositions, while HTK and Celsior do not contain any type of oncotic agent. Polyethylene glycols (PEGs) are non-immunogenic, non-toxic and water-soluble polymers, which present a combination of properties of particular interest in the clinical context of ischemia-reperfusion injury (IRI): they limit edema and nitric oxide induction and modulate immunogenicity. Besides static cold storage (SCS), there are other strategies to preserve the organ, such as the use of machine perfusion (MP) in dynamic preservation strategies, which increase graft function and survival as compared to the conventional static hypothermic preservation. Here we report some considerations about using PEG35 as a component of perfusates for MP strategies (such as hypothermic oxygenated perfusion, HOPE) and its benefits for liver graft preservation. Improved liver preservation is closely related to mitochondria integrity, making this organelle a good target to increase graft viability, especially in marginal organs (e.g., steatotic livers). The final goal is to increase the pool of suitable organs, and thereby shorten patient waiting lists, a crucial problem in liver transplantation.
This study was supported by grant from Ministerio de Ciencia e Innovación, reference PID2019-104130R B-I00 awarded to E.F.-P., the European Comission H2020-MSCA-ITN-ETN-2016 “FOIE GRAS – Metabolism and the Liver-Gut Axis in Non-Alcoholic Fatty Liver Disease” and the Marie Curie Fellow to Rui Teixeira da Silva. The authors thank Veronica Raker for revising the manuscript.