Towards Clinical Xeno-islet Transplantation: Experience in Pig-to-primate Model and Pig Production

摘要

Xenotransplantation into humans is defined as "any procedure that involves the direct transplantation, implantation, or infusion into a human recipient of live cells, tissues, or organs from a non-human animal source; or indirect exposure, where humanbody fluids, cells, tissues, or organs that have had ex vivo contact with live non-human animal cells, tissues, or organs are administered." This presentation addresses the first part of this definition, with the main focus on insulin-producing pancreatic islets. The rationale of Xenotransplantation is based on the successes in clinical transplantation during the last decades, after immunosuppressive regimens to prevent rejection had substantially improved with respect to adverse side effects and clinical acceptance. Kidney and heart transplantation made a substantial boost in the eighties of the last century, after the immunosup-pressant cyclosporine reached the market. The major hurdle in further expansion of organ transplantation is the limited availability of human cadaveric donors: hence, living donor kidney transplant programs contribute nowadays a major part of clinical transplantation. An alternative is the search of other species, and the pig species has been selected being most suitable. Major reasons of selecting the pig species are breeding and husbandry (short generation time and large litter size), physiologic compatibilities (e.g., kidney function like glomerular filtration rate, cardiac output, and function of porcine-derived insulin in diabetes patients), possibilities of genetic modification and cloning, and acceptance from an ethical point of view.