The shortage of suitable donor organs remains one of the greatest challenges in transplantation medicine. In Germany alone, around 8,200 people are currently waiting for a donor organ. At Hannover Medical School (MHH), a partner institution of the German Center for Lung Research (DZL) at the BREATH site, the new research project “Xenotransplantation in Lower Saxony” (XeNid) has now been launched. Its aim is to establish the prerequisites for using genetically modified pig organs as temporary replacements until a suitable human donor organ becomes available. The State of Lower Saxony and the Volkswagen Foundation are funding the four-year project with approximately €4 million through the “zukunft.niedersachsen” funding program.
Several researchers from the DZL’s BREATH site are involved in XeNid, including PD Dr. med. Tobias Goecke, PD Dr. Fatih Noyan, and Dr. Robert Ramm. The project builds on previous research conducted as part of the BREATH Junior Research Group on Xenogeneic Lung Transplantation, including work on organ perfusion. These studies established important experimental foundations on which the new XeNid project will now build.
Pigs are generally well suited as potential organ donors because of their anatomical and physiological similarities to humans. Additional advantages include the possibility of selecting donor animals to match individual human recipients and genetically modifying the animals. Combined with novel immunosuppressive strategies and improved organ preservation, these approaches may help prevent immediate rejection of animal organs by the human immune system.
The MHH team is pursuing several approaches. For patients with acute liver failure, for example, the researchers aim to develop a form of temporary liver support using genetically modified pig livers. The project also includes new concepts for regenerative implants based on pig heart valves and ex vivo lung perfusion. At the same time, key questions concerning immune responses, infection risks, transplantation techniques, and ethical frameworks must be addressed. Patient organizations will therefore also be involved in the development process.
A case report recently published in The Lancet illustrates how the potential of xenotransplantation is becoming increasingly tangible. A patient with end-stage kidney disease received a genetically modified pig kidney that provided kidney function for 271 days—approximately nine months—without the need for dialysis. Xenotransplantation was subsequently discontinued, and the patient later received a human donor kidney in a successful transplant.
The case also highlights the significant challenges that remain. No clinically relevant transmission of pig pathogens occurred, and no problematic immune sensitization against the subsequent human donor kidney was observed. However, the xenograft developed vascular damage over time and eventually lost its function. “This case clearly demonstrates that xenotransplantation can, in principle, serve as a bridge to human organ transplantation. At the same time, it shows which immunological and biological mechanisms we still need to address to maintain organ function over the long term,” says Dr. Robert Ramm.
With XeNid, the preliminary work carried out through projects of the BREATH Junior Research Group will now be continued within a larger interdisciplinary research consortium, laying the groundwork for future clinical applications. In particular, the combination of organ perfusion, transplantation medicine, and immunology opens up new opportunities for advancing xenotransplantation.
Source: BREATH
