Organ transplantation saves thousands of lives every year. The surge in demand with a persistent organ shortage represents a major healthcare challenge. If all patients were transplanted, the NHS could save £152m per year. Nowadays, older and ‘higher risk’ deceased donor organs are considered with an increased chance of non-function and graft failure.
Uncertainty which organ to accept or not has led to increased discard rates. Better clinical parameters predicting outcomes and novel technologies to assess, condition and repair such organs are crucial.
1) Develop a robust organ viability assessment tool, including identification of relevant biomarkers of organ quality, genetic profiles and digital pathology, using an integrated –omics platform (proteomics, metabolomics) and collected samples of the national QUOD biobank in Oxford (more than 2,000 donors, 195,500 biobank items) linked with the UK transplant registry;
2) Recondition donor organs with Normothermic Machine Perfusion. NMP restores homeostasis in organs during preservation whilst outside the body. We have developed this concept and a new device for the liver (OrganOx metra®), currently in clinical trials. We will now apply NMP to condition discarded human livers and kidneys and compare function and molecular profiles with results from successfully transplanted organs;
3) Aim to repair injured organs with novel therapeutic approaches using cell therapy to release factors that may help regenerate function. After controlled infusion of stromal or immune regulatory cells during isolated ex-vivo NMP we will identify the site of homing and interactions of these cells with the injured organ, potentially reducing inflammation and immunogenicity whilst stimulating repair and immune modulation towards sustained function post-transplant. Re-assessment, using validated profiles (1), after conditioning (2) and cell therapy (3) will demonstrate which of the previously discarded organs can be transplanted in first-in-man studies;
4) Islet transplantation to cure diabetes mellitus has achieved considerable clinical success. The next challenge is to make it suitable for diabetic children by transplanting without significant suppression of the immune system through medication. This involves developing techniques for human islets enhancing survival by implantation of a novel islet device;
5) We will also commence first-in-man trials of tissue engineered mucous membranes as a novel means of repairing mucosa lost through disease, trauma or after head and neck cancer resection. Functional movement will be a great benefit where it has been impaired by disease or trauma.