Animal models in xenotransplantation

The severe shortage of donor organs has provided a strong impetus to push t he investigation into the use of animal organs for humans. Xenotransplantat ion will not only benefit patients, but also represents a unique and potent ially profitable business opportunity. However, there are many barriers to successful clinical xenotransplantation, including immunological barriers, physiological incompatibility, zoonosis and ethical concerns. This overview will focus on currently available animal models used in attempts to break through the immunological barriers to xenotransplantation. There are many a dvantages to using small animal, namely rodent, models in xenotransplantati on research. For example, the use of the mouse model allows the use of knoc kout mice and careful dissection of rejection mechanisms at the molecular l evel. The following models can be used to study hyperacute rejection (HAR): guinea-pig-to-rat, mouse-to-rabbit, guinea-pig-to-mouse, rat-to-presensiti sed mouse and rat-to-alpha-Gal knockout mouse. The hamster-to-rat, mouse-to -rat and rat-to-mouse models are commonly used to study acute vascular reje ction. Large animal models are complex and expensive, but they are more rel evant to clinical xenotransplantation. Based on experiments using transgeni c pig-to-primate models, HAR can be overcome. However, acute vascular rejec tion remains a major barrier at the present time. A pig cartilage-to-monkey model has been developed to study chronic rejection. Other novel models su ch as pig venous segment-to-monkey model and rat-to-primate model may repre sent viable options to study immunological barriers following xenotransplan tation. Like many other medical breakthroughs, animal research will continu e to make enormous contributions towards the eventual success of xenotransp lantation.