- Dr. Elaine Holmes, Principal Investigator
- Dr. Gerrard Murphy, Co-Investigator
- Dr. Hector Vilca-Melendez, Co-Investigator
- Imperial College, London, UK
- Metabolic Assessment of Human Donor Livers in Transplantation
The success of liver transplantation has led to increased use of ‘marginal’ grafts and an urgent need to find reliable ways of assessing donor livers both at retrieval and immediately after implantation. Nuclear Magnetic Resonance (NMR) based analysis has been shown to be a good technique for obtaining metabolic profiles of disease and toxicity and for identifying biomarkers of tissue dysfunction. In particular, the technique of Magic Angle Spinning (MAS) NMR spectroscopy combined with computer-based pattern recognition techniques (PR) offers a unique holistic and objective approach to the assessment of donor liver function pre- and post-transplantation.
Our overall aim is to provide a holistic approach for the assessment of the ‘quality’ of donor livers pre- and post-transplantation with a view to maximizing the success of post-operative graft function and survival. We want to not only enlarge the pool of available donors but also establish criteria for the early detection of post-operative hepatic dysfunction. We will achieve our purpose by using a combination of conventional high resolution NMR spectroscopy and MAS proton nuclear magnetic resonance (1H NMR) spectroscopic analysis together with ultra high-performance liquid chromatography-MS to obtain a metabolic "fingerprint" of the donor liver at its retrieval, after cold storage and reperfusion and following its implantation in the recipient. Metabolic "fingerprints" of biopsy samples will be obtained from donor livers and correlated with graft survival. In addition to the biopsy sample, a series of blood, urine and bile samples will be obtained during the course of the transplant procedure in order to explore any indicators of subsequent graft function. Having devised a successful strategy for identifying suitable donor livers, we would propose to extend the technology to other organs.