First visit to Igelosa to meet Prof. Stig Steen, a pioneer of ex-vivo lung perfusion (EVLP). This leads to a new way of thinking and a shift of focus towards organ perfusion.
We demonstrate that in humans, EVLP mobilises the donor immune compartment and can be used to remove donor leukocytes before lung transplantation.
We publish the first multicentre clinical trial in collaborartion with Igelosa, and Skane Hospital, Sweden, demonstrating that EVLP of marginal donor lungs does not lead to adverse outcomes following lung transplantation.
We develop a new hypothesis that EVLP removes donor leukocytes (that contribute to rejection). We perform a complex evaluation and publish a seminal paper demonstrating that EVLP alters the donor immune environment, improving clinical outcome after transplant.
We develop a ‘ground-up’ build of a donor kidney perfusion system, with a focus on physiological perfusion (replicating the in-vivo environment). We then publish our first kidney paper, demonstrating that our kidney protocol mobilises the donor immune compartment in the kidney, which will reduce reperfusion injury post-transplant.
Given the role of donor leukocytes in rejection, we then designed and tested a new donor-kidney flush protocol. In this study, we demonstrated that flushing the renal vasculature immediately prior to transplant removed billions of donor leukocytes, many of which play a pathological role in rejection.
The team focus on designing and testing a new approach to limb perfusion, again focusing on recapitulating the in-vivo environment. We publish our first limb paper reporting our vascular flush protocol that should be used to prepare the limb before transplant.
Working with Prof Steen, we evaluate a novel device that can increase safe preservation of the donor heart from 4 hours to 24 hours. We publish a paper in Frontiers of Immunology, demonstrating that this device and protocol significantly immunodeplete the donor heart (removes donor leukocytes) and reduces graft infiltration after transplant.
The team evaluate how perfusion alters cell signalling, and complete a comprehensive proteomic analysis of a wide range of genes. In this study, we demonstrate that perfusion drives mitochondrial salvage and activates cell survival pathways.
In our previous work we identified changes to several immune and gene related parameters. We recognised unique processes in organs that did not recover during perfusion. We then evaluated if molecules associated with non-recovery could be used as a prognostic indicator during perfusion.
Back to the limb, we completed a randomised preclinical trial to define the optimal parameters for limb perfusion. This world-first data highlighted the importance of physiology during perfusion.
Back to the science, we assess if our limb NMP protocol has ancillary benefits by removing donor leukocytes that contribute to rejection. We publish a paper demonstrating that our protocol can be used to remove billions of donor cells.
We publish a preclinical study demonstrating that the addition of a kidney on a limb limb perfusion circuit improves preservation by preventing acidosis and reducing inflammatory burden.