XENO-LUNG TRANSPLANTATION

Every year, thousands of patients worldwide die on the waiting list for a human donor organ. In order to counteract the underlying shortage of organ donors, efforts are being made to provide animal organs for human transplant patients. Efforts to transplant organs from different species are referred to as xenotransplantation. Technically, the transfer of animal tissue or organs to a human recipient is possible without any problems, provided that the transplant corresponds in size, shape and physiology to the human structure to be replaced. This is the case, for example, when porcine organs are used - provided the donor pig is the right size. However, as soon as the xenogeneic transplant comes into contact with the blood of the human recipient after implantation, an extremely strong immune reaction occurs. This far exceeds the immune response to be expected in the context of an analogous allotransplantation and consists of cellular and humoral rejection mechanisms on the one hand and an excessive activation of the recipient's blood coagulation system on the other. Both aspects have not yet been fully researched. However, a detailed understanding and a reliable overcoming of these hurdles in the interests of the many patients who would be enabled to live a long and pain-free life through the safe provision of a fully functional and healthy animal donor organ is absolutely essential and has therefore become the declared goal of our working group!

Projects:

DZL-JRG "Xeno-lung transplantation"

The main focus of our current projects is the preparation of preclinical porcine xenogeneic lung transplantation studies in the large animal model. Against this background, we are currently focusing on the following research priorities:

1) The identification of necessary as well as target-oriented genetic modifications of the donor pigs

2) The establishment of suitable ex vivo perfusion modelsto analyze the human-relevant immune potential of pig lungs

3) The development of optimized therapeutic strategies for immunosuppression, immunomodulation and tolerance induction after xenotransplantation

Range of methods:

The current analyses of the interaction profile between human blood and immune components and porcine pulmonary endothelial cells are carried out in the context of circulation experiments in a microflow chamber and ex vivo perfusion experiments using anatomical porcine lung preparations.