The influence of DAMPS during warming machine perfusion of human donor livers prior to clinical transplantation

• Applicant: Professor Dr. Dieter Paul Hoyer
• Subject Area: General and Visceral Surgery
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 562407350

Liver transplantation is nowadays an established therapeutic procedure. The quality of the donor liver plays a critical role in the success of the transplant. Machine perfusion has shown promise in improving organ quality. This project focuses on the by us clinically established technique of Controlled Oxygenated Rewarming (COR). This method aims to improve donor organ quality by minimizing damage to liver cell structures and maintaining optimal energy homeostasis, as demonstrated by us in preliminary work. The transcriptome analyses we have performed to date suggest the influence of specific metabolic pathways. We postulate that perfusion affects danger-associated molecular pattern molecules (DAMPs) and influences ischemia-reperfusion injury through the innate immune response. This project aims to gain a deeper understanding of the molecular processes involved. Human samples of donor livers, clinical machine perfusate and recipient serum will be extensively analyzed to characterize the effects of the COR method on the graft. Particular attention will be paid to the molecular level, with identification of DAMPs and their role in the innate immune response being of central importance. Methodologically, the focus is on specific studies of the transcriptome on the innate immune response, as well as proteomic analyses to complete our understanding of translation. Validation is planned by immunohistochemical staining of existing human histological sections. Overall, this project aims to refine COR machine perfusion methodology in liver transplantation and deepen our understanding of the underlying processes.

• DFG Programme: Research Grants
• International Connection: Netherlands
• Cooperation Partner: Professorin Eva Cuypers