Machine perfusion of donor organs for transplantation

Abstract

The ever‐widening gap between organ supply and demand has resulted in an organ shortage crisis that affects patients all over the world. For decades, static cold storage (SCS) was the gold standard preservation strategy because of its simplicity and cost‐effectiveness, but the rising unmet demand for donor organ transplants has prompted investigation into preservation strategies that can expand the available donor pool. Through ex vivo functional assessment of the organ prior to transplant, newer methods to preserve organs such as perfusion‐based therapy can potentially expand the available organ pool. This review will explain the physiologic rationale for SCS before exploring the advantages and disadvantages associated with the two broad classes of preservation strategies that have emerged to address the crisis: hypothermic and normothermic machine perfusion. A detailed analysis of how each preservation strategy works will be provided before investigating the current status of clinical data for each preservation strategy for the kidney, liver, pancreas, heart, and lung. For some organs there is robust data to support the use of machine perfusion technologies over SCS, and in others the data are less clear. Nonetheless, machine perfusion technologies represent an exciting frontier in organ preservation research and will remain a crucial component of closing the gap between organ supply and recipient demand.

Potential options to expand the intestinal donor pool: a comprehensive review

“…Despite the clinical usage of machine perfusion for kidneys in the 1970 s, this preservation strategy virtually disappeared in the 1980 s due to the development of adequate preservation solutions for simple static cold storage and the simplicity of this preservation [33]. Recently, supported by the technical innovations and the interest of the industry, machine perfusion became of increasing interest in solid organ transplantation once more [34]. These developments were also initiated by the deteriorating profile of the donor organs that could no longer be adequately preserved by simple cold storage.…”

Development of a Novel Perfusable Solution for ex vivo Preservation: Towards Photosynthetic Oxygenation for Organ Transplantation

“…Some of these systems are based on extracorporeal oxygenation devices, where erythrocytes are oxygenated in a dynamic system that allows them to recirculate through the organ vascular network. Although recent clinical data support their safety and efficacy ( Xu et al, 2020 ; Tatum et al, 2021 ), the use of blood generates additional complications, because it is not always available on site, has a relative short preservation time and requires the inclusion of a membrane oxygenator, which substantially increases the total cost ( Aburawi et al, 2019 ). Additionally, blood recirculation generates hemolysis, which can be toxic as free hemoglobin can cause inflammation and oxidative stress ( Gkoumassi et al, 2012 ; Bodewes et al, 2021 ), thus the development of novel perfusable solutions for ex vivo oxygenation is an active field of research.…”

Adipose-Derived Stem/Stromal Cells in Kidney Transplantation: Status Quo and Future Perspectives

“…The proposed mechanisms of action are enhanced nitric oxide (NO) production, preserved adenosine triphosphate (ATP) synthesis, and increased resistance to oxidative stress, eventually determining reduced intra-vascular resistive index (RI), better intra-parenchymal perfusion, and less tissue damage [ 22 ]. Questioning routine organ preservation under hypoxic and hypothermic conditions, some authors have advocated the use of oxygenated preservation techniques [ 23 ] and sub-normo-thermic (SMP) or normo-thermic machine perfusion (NMP) [ 24 ]. Theoretical advantages of controlled oxygenation and heating are better mitochondrial viability and function, decreased production of reactive oxygen species (ROS), and reduced activation of cell death programs [ 24 ].…”

“…Questioning routine organ preservation under hypoxic and hypothermic conditions, some authors have advocated the use of oxygenated preservation techniques [ 23 ] and sub-normo-thermic (SMP) or normo-thermic machine perfusion (NMP) [ 24 ]. Theoretical advantages of controlled oxygenation and heating are better mitochondrial viability and function, decreased production of reactive oxygen species (ROS), and reduced activation of cell death programs [ 24 ]. Whilst the usefulness of isolated organ oxygenation has not been confirmed in human studies [ 23 ], encouraging results have been obtained with oxygenation during HMP [ 25 ] and NMP [ 26 ].…”