The Emerging Importance of Liver Sinusoidal Endothelial Cells in Regulating Injury during Machine Perfusion of Deceased Liver Donors.

While majority of liver transplants worldwide continue to be performed using deceased donor organs, the demands for donor livers continues to exceed the current supply. In an attempt to maximize the number of potentially usable donor livers and expand the current donor pool, there is intense global research by various groups exploring the role of machine perfusion in the liver transplantation, particularly with respect to the machine perfusion of extended-criteria liver donors. In this review, the authors summarize the current field of machine perfusion strategies as applied to deceased donor liver transplantation and how therapeutic targeting of the liver sinusoidal endothelial cell may improve the quality of donor livers.

Bhogal RH ，Mergental H ，Mirza DF ，Afford SC ... -  《-》

Organ Preservation in Liver Transplantation.

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. Various strategies to cope with the donor shortage problem and to increase the use of suboptimal grafts have been explored. Machine perfusion has been applied ex situ to liver grafts in the effort to improve static cold-storage preservation. If a more extensive application of this technology confirms the preliminary results, machine perfusion will become crucial in increasing the donor pool as well as improving recipients' outcomes. In this review, the authors focused on the evolution of machine perfusion, from the first animal experiences to the latest evidence in humans, highlighting the pros and cons as well as the potential clinical applications of various types of machine.

Burra P ，Zanetto A ，Russo FP ，Germani G ... -  《-》

Hypothermic machine perfusion in liver transplantation.

A finite supply of donor organs has led many transplant centers to accept marginal liver allografts with increasing frequency. These allografts may be at higher risk of primary nonfunction, early allograft dysfunction, and other recipient complications following liver transplantation. Machine perfusion preservation is an emerging technology that limits ischemia/reperfusion injury associated with preservation and may lead to improved outcomes following transplantation. Increased used of machine perfusion in liver preservation may permit an expansion of the donor pool. In this review, we examine the major clinical experience of hypothermic machine perfusion in human liver transplantation.Liver Transplantation 24 276-281 2018 AASLD.

Quillin RC 3rd ，Guarrera JV 《-》

Oxygenated hypothermic machine perfusion after static cold storage improves endothelial function of extended criteria donor livers.

Lack of oxygen and biomechanical stimulation during static cold storage (SCS) of donor livers compromises endothelial cell function. We investigated the effect of end-ischemic oxygenated hypothermic machine perfusion (HMP) on endothelial cell function of extended criteria donor (ECD) livers. Eighteen livers, declined for transplantation, were transported to our center using static cold storage (SCS). After SCS, 6 livers underwent two hours of HMP, and subsequent normothermic machine perfusion (NMP) to assess viability. Twelve control livers underwent NMP immediately after SCS. mRNA expression of transcription factor Krüppel-like-factor 2 (KLF2), endothelial nitric oxide synthase (eNOS), and thrombomodulin (TM) was quantified by RT-PCR. Endothelial cell function and injury were assessed by nitric oxide (NO) production and release of TM into the perfusate. In HMP livers, mRNA expression of KLF2 (p = 0.043), eNOS (p = 0.028), and TM (p = 0.028) increased significantly during NMP. In parallel, NO levels increased during NMP in HMP livers but not in controls. At the end of NMP cumulative TM release was significantly lower HMP livers, compared to controls (p = 0.028). A short period of two hours oxygenated HMP restores endothelial cell viability after SCS and subsequent normothermic reoxygenation of ECD livers.

Burlage LC ，Karimian N ，Westerkamp AC ，Visser N ，Matton APM ，van Rijn R ，Adelmeijer J ，Wiersema-Buist J ，Gouw ASH ，Lisman T ，Porte RJ ... -  《-》

Impact of machine perfusion preservation of liver grafts from donation after cardiac death.

Because of the critical shortage of deceased donor grafts, using a donation after cardiac death (DCD) donor is an important resource. However, the ischemic damage of those DCD grafts jeopardizes organ viability during cold storage. Maintaining organ viability after donation until transplantation is important for optimal graft function and survival. This review describes the effective preservation in transplantation for DCD livers. Concepts and development of machine perfusion for DCD liver grafts to reduce ischemia/reperfusion injury are discussed. Despite the fact that hypothermic machine perfusion might be superior to static cold preservation, DCD livers are exposed to hypothermia-induced damage. Recently, some groups introduced the beneficial effects of normothermic or subnormothermic machine perfusion in DCD liver preservation and transplantation.

Matsuno N ，Uchida K ，Furukawa H 《-》