A significant concern after a person receives an organ transplant from a donor is antibody mediated rejection (AMR) - a process by which antibodies in the recipient can cause their immune systems to reject and damage the donor organ. This can lead to loss of the transplanted organ and even death in some cases.
It has been difficult to create human experimental models of rejection and as a result researchers have had little opportunity to investigate therapies that might reduce the risk of this devastating complication and to elucidate new mechanisms. However, King’s researchers have today published a clinically relevant, reproducible, and translational model of AMR using human kidneys and warm machine perfusion technology, for what is believed to be the first time.
The study, published by the prestigious translational science journal The Lancet eBioMedicine, (Lancet Discovery Science) was authored by post-doctoral researcher and transplant trainee, Pankaj Chandak and senior authors, Professors Anthony Dorling and Nizam Mamode alongside colleagues in the School of Immunology & Microbial Sciences at King’s College London, Guy’s and St Thomas’ Trust NHS Foundation Trust and King’s Health Partners.
By connecting a human organ (offered for research purposes) to a bypass machine and circulating warm blood-based solutions through the organ (known as warm machine perfusion), then deliberately adding antibodies and complement and coagulation factors to the circuit, the researchers can artificially induce and simulate AMR. In so doing they may be able to study transplant rejection mechanisms more closely and - it is hoped – gain greater insight into how this condition may be prevented.
Most notably, the model may allow researchers to investigate and test organ specific targeted therapy. Strong immunosuppressors are often used to prevent donor organ rejection, but use of these drugs puts recipients at risk of other complications such as sepsis. Targeted organ specific therapeutics, however, may allow doctors to treat only the intended organ, lessoning the risks posed to the body.
The development of an experimental human model of transplant rejection using warm machine perfusion may allow testing of targeted organ specific therapy and to gain further mechanistic insight into this process. We may then also investigate repair and regeneration interventions in these rejected, injured organs. This could then hopefully be used to help real patients” – Pankaj Chandak, Lead Author