Towards ex vivo repair of damaged donor kidneys

The shortage of donor kidneys is a worldwide problem. One possibility to increase the donor organ pool is to improve the quality of suboptimal donor kidneys. For this reason, an increasing amount of research is being performed on the subject of machine perfusion, a technique during which an organ is connected to a perfusion circuit. Apart from the fact that this technique can be used to bridge the period between donation and actual transplantation, it also provides the opportunity for active interventions to an isolated organ. The first part of my thesis focuses on a cellular intervention during normothermic (37 degrees) machine perfusion with mesenchymal stromal cells. The aim was to determine if it was technically feasible to administer mesenchymal stromal cells, cells with regenerative capacities, during normothermic machine perfusion and what effect these cells had on the donor kidney. It proved to be feasible to administer these cells in such way that a proportion remained detectable after machine perfusion. In a porcine autotransplantation model, mesenchymal stromal cells did not affect early graft function, but further research is necessary to determine if these cells could have a beneficial effect on longer term graft function of the donor kidney. The second part of my thesis focuses on the use of different perfusion solutions and oxygen carriers during normothermic machine perfusion. From these experiments it can be concluded that the composition of the perfusion solution, as well as the choice for a specific oxygen carrier, has a significant impact on kidney function and injury markers during normothermic machine perfusion.