Aims and status of the German DFG ‐ Transregio Research Group Xenotransplantation

Abstract

Allotransplantation is the therapy of choice for endstage diseases. Due to the organ shortage, three times respectively twice as many patients are currently waiting for kidneys or hearts as are actually transplanted annually in Germany. Consequently, the mortality rate on the heart transplant list is around 16%; if patients have to wait more than 24 months for a kidney, the graft survival after 10 years will be less than half when compared to those who are able to receive an organ within 6 months. Therefore, porcine xenotransplantation of kidneys and hearts will be a very much needed alternative clinical technique – including (porcine) xenogenic islet cell transplantation for diabetic patients with hypoglycaemic attacks – a large number of persons, if one considers that the number of people suffering from diabetes worldwide increased by nearly 50% over the last decade.Of course, much more work is needed before clinical xenotransplantation will become a safe and long lasting alternative. The α(1,3)‐galactosyltransferase KO, PERV C free pigs – held in specific pathogen free units – must express several human transgenes, like a complement regulator molecule (in order to suppress non Gal‐AB's) and HLA‐E (protection from NK‐cell cytotoxicity). Some kind of accommodation will be necessary (e.g. via Hemoxygenase‐1 or PDL‐1 – a negative costimulatory receptor which also increases the CD4+ CD25high Fox p3+ subset). An overexpression of thrombomodulin (TM) would finally be necessary in order to overcome the disparity between porcine (TM) and human (Thrombin) proteins and possibly avoid microvascular thrombotic disease.And to top all these desires of a clinical transplant specialist, all the genetic engineering should be achieved in close connection within one chromosome, preferably an artificial one, in order to make all these changes hereditary.The just mentioned strategies are the main topics of the DFG‐Transregio Research Group. The following abstracts will highlight the respective progress and will also inevitably evaluate arising problems. International leaders in our field will give their results and opinion – an interchange which is necessary within the small but very active xenotransplantation research field.It is my sincere belief that a clinical scenario of xenotransplantation will be possible in the near future.