Biology of xenogeneic cell and organ transplantation - from bench to bedside
Solid organ and cell transplantations, including pancreatic islets, are the treatment of choice for terminal diseases and several chronic disorders. Due to the severe shortage of appropriate human organs and tissues for allotransplantation, alternative strategies are required. Xenotransplantation of porcine tissues or organs is a reasonable option, since immunological hurdles and functional incompatibilities can be overcome by precise genetic engineering of donor pigs or by the development of specific matrices and devices for xenotransplantation of cells.
We have established an interdisciplinary consortium of basic and translational scientists, such as immunologists, genetic engineers, cell physiologists, virologists and transplant surgeons, to develop pig-to-primate xenotransplantation from the experimental studies to clinical application. Our research programme is structured into three main-areas:
(A) understanding and regulating immunity to xenografts
(B) production of novel multi-transgenic pigs to prevent endothelial cell
activation, inflammation, thrombosis and immune rejection
(C) preclinical and clinical xenotransplantation
A major focus is islet xenotransplantation, where studies extend from preclinical humanised mouse-models through non-human primates to clinical applications. Multi-transgenic pig-to-primate heart and kidney transplantation experiments aim at a 90 day graft survival rate in a life-supporting system within the next 4 years, paving the way for clinical translation of pig-to-primate xenotransplantation.