The use of organs from donors after circulatory death (DCD) has been recommended as one strategy to enlarge the donor pool and raise the transplant rate. However, DCD allografts had higher incidence of early post-transplant dysfunction. The general aim of this research project was to develop clinical and experimental strategies to reduce the incidence of early post-transplant dysfunction of kidney and liver allografts from DCD. First the ability of a clinical scoring system based on donor data for identifying DCD kidneys with high-risk of post-transplant dysfunction was evaluated using the Oxford and the UK National DCD kidney transplant cohorts. This works suggest that stratification of DCD kidneys before transplantation might allow early identification of kidneys in which lower graft function and survival could be expected if any additional therapeutic intervention is implemented. Second, as it has been suggested that hypothermic machine perfusion (HMP) may protect DCD kidneys from additional preservation injury and improve their outcome after transplantation, this work explored the benefit of HMP as preservation technique fo DCD kidneys in Oxford and discusses the potential of this technique for reducing the incidence of post-transplant dysfunction in DCD kidneys. The Oxford. Liver Group has provided evidence of the benefit of preservation with normothermic machine perfusion (NMP) on post-transplant function and survival of DCD liver allografts. In this work, the molecular mechanisms associated with this benefit were characterized using micro array technology. This analysis suggests that the beneficial effect ofNMP may be associated with the induction of the ischaemic preconditioning phenomenon and highlights a group of genes with potential for gene therapy. Finally, this works provides the "proof-of-concept" that the use of a non-mammalian viral vector for gene transfer of kidneys and livers during conventional cold preservation is feasible and is not associated with additional tissue injury.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:572681 |
| Date | January 2012 |
| Creators | Plata-Muñoz, Juan José |
| Contributors | Friend, Peter ; Fuggle, Susan V. |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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