Normothermic liver preservation: a new paradigm?

Abstract

Summary Despite increasing donor numbers, waiting lists and pre‐transplant mortality continue to grow in many countries. The number of donor organs suitable for liver transplantation is restricted by cold preservation and ischemia‐reperfusion injury (IRI). Transplantation of marginal donor organs has led to renewed interest in new techniques which have the potential to improve the quality of preservation, assess the quality of the organ and allow repair of the donor organ prior to transplantation. If successful, such techniques would not only improve the outcome of currently transplanted marginal livers, but also increase the donor pool. Experimental evidence suggests that preservation under near physiological conditions of temperature and oxygenation abrogates IRI. Normothermic perfusion maintains the organ in a physiological state, avoiding the depletion of cellular energy and the accumulation of waste products, which occurs with static cold storage. It enables viability assessment prior to transplantation thereby reducing the risk of transplanting inherently marginal organs. Here we review the use of normothermic machine perfusion as a means of organ preservation.

Optimising organs for transplantation: is normothermic machine perfusion the answer?

“…Research efforts have focused on overcoming the limitations of cold storage with a move toward normothermic machine perfusion (NMP). Organs are preserved under near physiological (as opposed to hypothermic) conditions to attenuate ischemic injury caused by prolonged cold preservation (from static cold storage (SCS)) and potentially maintain all aspects of graft function throughout the preservation process [4]. In addition, the method of storage in NMP allows for pre-transplant assessment of organ function and thereby viability to predict suitability for implantation, and delivery of potential agents (such as stem cells) to further ameliorate the IRI [5].…”

“…These include basic roller pumps, oxygenators, and heat exchangers [4]. Centrifugal pumps exhibit preferable pressure and flow characteristics and are more resistant to hemolysis.…”

Graft Reconditioning before Liver Transplantation

“…To overcome this situation, several ways to increase the donor pool have been suggested, with the acceptance of livers of limited quality being the predominant way of making additional organs available [9,10,11]. Subsequently, the risk associated with LT has increased as such organs are more prone to ischemia/reperfusion injury after implantation [12,13,14,15]. This can lead to severe or even extreme allograft injury, resulting in increased morbidity and mortality immediately post transplantation [16].…”

New Approaches to Cryopreservation of Cells, Tissues, and Organs

“…Short organ preservation times impose numerous constraints on transplantation, contributing to the organ shortage, exacerbating graft rejection, and limiting the length and quality of life of transplant recipients [1, 3-13]. In addition to their role in helping to address organ shortage, advances in organ banking stand to greatly expand options for donor-recipient matching [1, 3, 6, 7] and equitable allocation; enhance screening for transmissible diseases and malignancies [1, 8-10]; decrease costs and enable flexible scheduling of surgeries [1, 14]; and allow assessment of organ quality before transplantation [3, 11-13].…”

“…In addition to their role in helping to address organ shortage, advances in organ banking stand to greatly expand options for donor-recipient matching [1, 3, 6, 7] and equitable allocation; enhance screening for transmissible diseases and malignancies [1, 8-10]; decrease costs and enable flexible scheduling of surgeries [1, 14]; and allow assessment of organ quality before transplantation [3, 11-13]. Advanced organ preservation modalities could even provide the opportunity for cutting-edge pretransplant interventions with the potential to improve transplant outcomes, including immunomodulation [15, 16] or gene therapy [17] and other approaches for functional augmentation [3, 18] in specialized laboratories [1, 4, 5]. Importantly, extending organ preservation times to just 5–7 days could allow current clinical immune tolerance induction protocols [19-22], which are showing promise in live kidney donation at several centers [23, 24] to be used in the context of deceased organ donation – reducing or eliminating the need for lifelong immunosuppression, thereby improving the lives of transplant recipients and saving the healthcare system in the USA roughly USD 100 million each year in costs for immunosuppression [25].…”