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Title: Machine perfusion for assessing and optimizing kidney and pancreas allografts
Author: Hamaoui, Karim
ISNI:       0000 0004 6495 4305
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2016
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Introduction: The predominate issue in transplantation today is the inadequate supply of suitable organs for an increasing number of patients on the transplant waiting lists. In efforts to address this demand there has been an increasing use of expanded-criteria and donation-after-cardiac death donor kidneys and pancreases, however these organs are at higher risk for reperfusion injury. Advances in organ preservation thus need to focus on techniques to assess and optimise organ viability prior to transplantation. Methods: This research focuses on organ viability assessment during preservation using rapid sampling micro-dialysis (rsMD); preconditioning organs with novel endothelial localising anticoagulants to prevent micro-vascular thrombotic complications; development of both novel hypothermic machine perfusion (HMP) solutions to minimise reperfusion injury, and HMP strategies that offer superior preservation of organ integrity compared to static cold storage (SCS). Using HMP and normothermic-reperfusion models of porcine and human kidney and pancreatic grafts, this project has investigated strategies addressing these themes. Results: rsMD can successfully provide detailed real-time information on tissue and organ viability during both SCS and HMP. Pre-conditioning grafts with novel localising anticoagulant proteins has been successful in ameliorating disturbances in macro and micro-vascular perfusion and graft microcvascular thrombosis, processes which play key roles in reperfusion injury and organ dysfunction. Separately the application of a novel adenosine/lidocaine based preservation solution in renal HMP preservation can potentially ameliorate reperfusion injury seen using conventional solutions. Post-ischaemic HMP reconditioning has been investigated in the context of recovering organs with an extreme period of SCS which may be a potential option to expand donor organ pools. Finally models of pancreatic HMP have been successfully established, opening the potential for organ viability assessment and optimization. Conclusion: This research has been successful in its overall objective to develop novel translational strategies that have high potential for clinical implementation. In doing so the goal would be to enable an expansion of the pool of acceptable donor organs by improving the methods used to determine and optimise their viability, specifically more effective preservation techniques and by addressing specific post-operative complications through graft preconditioning.
Supervisor: Papalois, Vassilios ; Darzi, Ara ; Habib, Nagy Sponsor: Imperial College Healthcare Charity ; Live Life Give Life
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral