Normothermic Ex vivo liver perfusion

The acceptance of liver transplantation as the standard of care for end-stage liver diseases has led to a critical shortage of donor allografts. To expand the donor organ pool, many countries have liberalized the donor criteria including extended criteria donors and donation after circulatory death. These marginal livers are at a higher risk of injury when they are preserved using the standard static cold storage (SCS) preservation techniques. In recent years, research has focused on optimizing organ preservation techniques to protect these marginal livers...

Introduction Ex vivo machine perfusion describes the technique where organs are continuously perfused and oxygenated extracorporeally (at physiological conditions) to maintain the organs' viability. To our knowledge, there are currently no reported studies describing ex vivo perfusion of a single hepatic segment. Here, we describe the development of a porcine ex vivo hepatic segmental perfusion model to demonstrate proof of concept and support further research into the ex vivo perfusion of the human liver using discarded tissue...

BACKGROUND: The successful implementation of end-ischemic normothermic machine perfusion (NMP) into clinical practice comes along with unusual demands for trained personnel and technical facilities in the implantation clinic. This creates an interest to bundle expertise and professional equipment for execution of MP at regional pump centers at the disadvantage of adding a second short period of cold preservation while sending the reconditioned grafts to the actual implant clinic. Differences of liver recovery upon reperfusion either immediately after NMP or after 3 h of cold storage subsequent to NMP should therefore be evaluated...

Ex-vivo perfusion describes the extra-corporeal delivery of fluid to an organ or tissue. Although it has been widely studied in the context of organ preservation and transplantation, it has also proven to be an invaluable tool in the development of novel models for translational pre-clinical research. Here, we review the literature reporting ex-vivo human liver perfusion experiments to further understand current perfusion techniques and protocols together with their applications. A computerised search was made of Ovid, MEDLINE, and Embase using the search words "ex-vivo liver or hepatic perfusion"...

BACKGROUND: Split liver transplantation permits the transplant of two recipients using a single donor liver. Liver splitting can be performed using the ex-vivo technique (more convenient), or the in-situ technique (shorter cold ischaemic time). We aimed to develop a technique for liver splitting during normothermic machine perfusion which combines the advantages of both techniques and permits graft assessment prior to transplant. METHODS: Human livers declined for transplantation were perfused at 36 °C using a modified-commercial perfusion machine...

The discrepancy between the number of patients awaiting liver transplantation and the number of available donors has become a key issue in the transplant setting. There is a limited access to liver transplantation, as a result, it is increasingly dependent on the use of extended criteria donors (ECD) to increase the organ donor pool and address rising demand. However, there are still many unknown risks associated with the use of ECD, among which preservation before liver transplantation is important in determining whether patients would experience complications survive after liver transplantation...

AL amyloidosis is a rare condition characterized by the overproduction of an unstable free light chain, protein misfolding and aggregation, and extracellular deposition that can progress to multiorgan involvement and failure. To our knowledge, this is the first worldwide report to describe triple organ transplantation for AL amyloidosis and triple organ transplantation using thoracoabdominal normothermic regional perfusion recovery with a donation from a circulatory death (DCD) donor. The recipient was a 40-year-old man with multiorgan AL amyloidosis with a terminal prognosis without multiorgan transplantation...

The development of surgical techniques, immunosuppressive strategies and new organ preservation methods have meant that transplant centers have to face the problem of an insufficient number of organs for transplantation concerning the constantly growing demand. Therefore, using organs from expanded criteria donors and developing new analytical solutions to find parameters or compounds that would allow a more efficient assessment of organ quality before transplantation are options for meeting this challenge...

PURPOSE OF REVIEW: The shortage of donor organs has led to the use of marginal extended criteria donor (ECD) livers to increase access to liver transplant. Ex-vivo machine perfusion allows for treatment and assessment of organs during preservation, potentially facilitating safe use of ECD livers at risk for worse clinical outcomes. This article reviews the latest published literature on the application of ex-vivo machine perfusion technologies in liver transplantation. RECENT FINDINGS: Multiple randomized controlled trials on the use of hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP) have been published in the past 5 years demonstrating improved graft function and decreased biliary complications after machine perfusion...

Transplantation is currently the treatment of choice for end-stage liver diseases but is burdened by the shortage of donor organs. Livers from so-called extended-criteria donors represent a valid option to overcome organ shortage, but they are at risk for severe post-operative complications, especially when preserved with conventional static cold storage. Machine perfusion technology reduces ischemia-reperfusion injury and allows viability assessment of these organs, limiting their discard rate and improving short- and long-term outcomes after transplantation...

BACKGROUND: Ex-vivo normothermic machine perfusion (NMP) preserves the liver metabolism at 37°C and has rapidly developed as a promising approach for assessing the viability and improving the performance of organs from expanded criteria donors, including fatty liver grafts. NMP is an effective method for defatting fatty livers when combined with pharmaceutical therapies. Pharmacological agents have been shown to facilitate liver defatting by NMP. OBSERVATIONS: This systematic review summarizes available pharmacological therapies for liver defatting, with a particular emphasis on defatting agents that can be employed clinically as defatting components during liver NMP as an ex vivo translational paradigm...

BACKGROUND: Controlled donation after circulatory death (cDCD) has become a standard in liver, kidney, and lung transplantation (LTx). Based on recent innovations in ex vivo heart preservation, heart transplant centers have started to accept cDCD heart allografts. Because the heart has very limited tolerance to warm ischemia, changes to the cDCD organ procurement procedures are needed. These changes entail delayed ventilation and prolonged warm ischemia for the lungs. Whether this negatively impacts lung allograft function is unclear...

INTRODUCTION: We developed a novel normothermic ex vivo porcine liver perfusion model with whole blood in order to have alternatives for animal experiments in the research and development of new local haemostatic agents. This study aims to assess the construct and content validity of this model. METHODS: In this study we performed two ex vivo experiments using nine livers and one in vivo experiment using six female Norsvin Topigs pigs: (1) ex vivo liver perfusion for establishing physiological blood parameters of the perfused liver and controlled heparinization, (2) ex vivo liver perfusion with a surgical injury and (3) a surgical liver injury in anaesthetized pigs with and without heparin...

The liver has been proposed as an important "immune organ" of the body, as it is critically involved in a variety of specific and unique immune tasks. It contains a huge resident immune cell repertoire, which determines the balance between tolerance and inflammation in the hepatic microenvironment. Liver-resident immune cells, populating the sinusoids and the space of Disse, include professional antigen-presenting cells, myeloid cells, as well as innate and adaptive lymphoid cell populations. Machine perfusion (MP) has emerged as an innovative technology to preserve organs ex vivo while testing for organ quality and function prior to transplantation...

UNLABELLED: Ex vivo normothermic machine perfusion (NMP) has improved organ preservation and viability assessment among heart, liver, and lung transplantation. However, literature regarding the application of NMP in human clinical kidney transplantation remains limited. Numerous kidneys, especially from donors with stage 3 acute kidney injury (AKI), are not utilized concerning the high rate of delayed graft function (DGF) and primary nonfunction. The present study investigated the impact of NMP (135-150 min) on short-term outcomes after kidney transplantation from deceased donors with AKI...

Acute liver failure (ALF) is a rare but devastating disease associated with substantial morbidity and a mortality rate of almost 45%. Medical treatments, apart from supportive care, are limited and liver transplantation may be the only rescue option. Large animal models, which most closely represent human disease, can be logistically and technically cumbersome, expensive and pose ethical challenges. The development of isolated organ perfusion technologies, originally intended for preservation before transplantation, offers a new platform for experimental models of liver disease, such as ALF...

Metabolic and toxic liver disorders, such as fatty liver disease (steatosis) and drug-induced liver injury, are highly prevalent and potentially life-threatening. To allow for the study of these disorders from the early stages onward, without using experimental animals, we collected porcine livers in a slaughterhouse and perfused these livers normothermically. With our simplified protocol, the perfused slaughterhouse livers remained viable and functional over five hours of perfusion, as shown by hemodynamics, bile production, indocyanine green clearance, ammonia metabolism, gene expression and histology...

Ex situ liver machine perfusion at subnormothermic/normothermic temperature is increasingly applied in the field of transplantation to store and evaluate organs on the machine prior transplantation. Currently, various perfusion concepts are in clinical and preclinical applications. Over the last 6 years in a multidisciplinary team, a novel blood based perfusion technology was developed to keep a liver alive and metabolically active outside of the body for at least one week. Within this manuscript, we present and compare three scenarios we were facing during our research and development (R&D) process, mainly linked to the measurement of free hemoglobin and lactate in the blood based perfusate...

Pancreas transplantation (PTx) is a curative treatment for people who live with the burden of a diagnosis of diabetes mellitus (DM). However, due to organ shortages and increasing numbers of patients being listed for PTx, new strategies are needed to increase the number of available grafts for transplantation. Static cold storage (SCS) is considered the gold standard for standard criteria organs. However, standard criteria donors (SCD) are becoming scarce and new strategies that can increase the rate of organ acceptance from extended criteria donors (ECD) are urgently needed...

The most common preservation technique for liver grafts is static cold storage. Due to the organ shortage for liver transplantation, extended criteria donation (ECD) allografts are increasingly used - despite the higher risk of inferior outcome after transplantation. Ex vivo liver machine perfusion has been developed to improve the outcome of liver transplantation, especially with ECD grafts, and is currently under evaluation in clinical trials. We performed a literature search on PubMed and ISI Web of Science to assemble an overview of rodent and porcine animal models of ex vivo liver machine perfusion for transplantation, which are essential for the present and future development of clinical liver machine perfusion...