Ex-situ machine perfusion across the organs; shared principles and transferable knowledge from clinical trials

Ex-situ machine perfusion (MP) technologies have revolutionised solid organ transplantation. Their core aims are to reduce ischemia-reperfusion injury (to improve recipient outcomes), prolong preservation times, and allow organ viability assessment. Different organs have unique considerations owing to their specific sensitivity to ischemia-reperfusion injury, as well as organ-specific logistical challenges and differing consequences of poor early graft function. Despite these differences, the core pathophysiologic processes underlying ischemia-reperfusion injury are shared, resulting in an organ-agnostic pathology of early graft dysfunction. The consequence of this shared biology is an opportunity for cross-organ learning. For example, the finding that hypothermic oxygenated MP ameliorates ischemia-reperfusion injury, and improves clinically relevant outcomes, has emerged as a consistent trend in randomised trials across multiple organs. In contrast, similar improvements in recipient outcomes have not been demonstrated in randomised trials of normothermic MP, whether applied to abdominal or thoracic organs. Such an integrated perspective could enable prioritisation of therapies for evaluation, particularly in settings where clinical trial activity is constrained, such as heart transplantation, by leveraging evidence generated in kidney transplantation where larger randomised trials are feasible and early graft dysfunction is more easily tolerated. In this integrated review we assess the clinical trial evidence for ex-situ MP across kidney, heart, liver, lung and pancreas. We focus on clinical trials reporting recipient outcomes, prolonged preservation and utilisation, highlighting themes for cross-organ learning.