Review of Current Machine Perfusion Therapeutics for Organ Preservation

Abstract

Because of the high demand of organs, the usage of marginal grafts has increased. These marginal organs have a higher risk of developing ischemia-reperfusion injury, which can lead to posttransplant complications. Ex situ machine perfusion (MP), compared with the traditional static cold storage, may better protect these organs from ischemia-reperfusion injury. In addition, MP can also act as a platform for dynamic administration of pharmacological agents or gene therapy to further improve transplant outcomes. Numerous therapeutic agents have been studied under both hypothermic (1–8°C) and normothermic settings. Here, we review all the therapeutics used during MP in different organ systems (lung, liver, kidney, heart). The major categories of therapeutic agents include vasodilators, mesenchymal stem cells, antiinflammatory agents, antiinfection agents, siRNA, and defatting agents. Numerous animal and clinical studies have examined MP therapeutic agents, some of which have even led to the successful reconditioning of discarded grafts. More clinical studies, especially randomized controlled trials, will need to be conducted in the future to solidify these promising results and to define the role of MP therapeutic agents in solid organ transplantation.

Hemorheological and Microcirculatory Factors in Liver Ischemia-Reperfusion Injury—An Update on Pathophysiology, Molecular Mechanisms and Protective Strategies

“…Machine perfusion will also provide a unique platform to deliver various ex vivo therapies without major systemic effects. Several laboratories have already investigated the benefits and limitations of allograft defatting, gene modulating agents, cytokine filtration, an-ti-inflammatory drugs, stem cells and extracellular vesicles as well as vasodilators in the setting of ex vivo machine perfusion [185]. Furthermore, machine perfusion driven viability assessment during HMP/HOPE or NMP may support clinical decision in the acceptance or rejection of marginal liver allografts [4,6,184].…”

Ex-Vivo Pharmacological Defatting of the Liver: A Review

“…The emergence of liver machine perfusion has allowed to push forward research on liver metabolism and offers a unique platform to evaluate therapeutics that may improve liver grafts function [6,28,29]. Published experiments for ex-vivo defatting of steatotic livers are summarized in Table 2.…”

Paulo Martins to serve as an Associate Editor of Artificial Organs

“…This project awarded him and his mentees several awards and impactful articles. [4][5][6] Last but not least, Dr. Martins has championed diversity/ equity efforts at local and national levels. He has dedicated efforts to increasing diversity by actively participating in diversity/minorities committees of the United Network of Organ Sharing (UNOS), American Society of Transplant Surgeons.…”

“…His team was the first to use machine preservation as a platform for gene silencing using siRNAs to alleviate organ ischemia reperfusion injury. This project awarded him and his mentees several awards and impactful articles 4‐6 …”