Normothermic machine perfusion of the liver (NMP-L) : a novel technique that permits the viability testing of donor livers and the targeted delivery of cellular therapy

Liver transplantation is a successful treatment for acute and chronic liver failure, yet the field faces challenges in the forms of deteriorating graft quality, increasing demand and more complex logistics. Normothermic machine perfusion is able to preserve donor livers for up to 24 hours and liver function can be objectively assessed during the perfusion process. Criteria that aim to establish donor liver viability have been developed through the perfusion of livers discarded for clinical use. The criteria are based upon metabolic and physiological parameters and have been tested within a clinical pilot study of five transplants using discarded organs. All grafts functioned immediately and all patients survived. Following on from this success, VITTAL (Viability testing and transplantation of marginal livers) - a Wellcome Trust funded trial - was designed and carried out. This saw the transplantation of 22 patients following 31 perfusions of discarded donor livers. The results validate the viability criteria and demonstrate that end-ischemic normothermic machine perfusion enables the safe transplantation of a significant proportion of currently unutilised livers and is associated with increased graft utilisation, extended preservation time and improved logistics. The use of Hemopure, a haemoglobin-based oxygen carrier, was also investigated and has been shown to have logistical, rheological and immunological advantages over packed red cells when used in the perfusion fluid. The final part of this thesis explored the use of machine perfusion devices to deliver cellular therapy to marginal donor livers. The results demonstrate the technique is feasible, with multipotent adult progenitor cells being delivered directly into the target organ allowing them to secrete a host of soluble factors that are known to have anti-inflammatory and immunomodulatory effects.