Animal models in xenotransplantation

Abstract

The severe shortage of donor organs has provided a strong impetus to push the investigation into the use of animal organs for humans. Xenotransplantation will not only benefit patients, but also represents a unique and potentially 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 advantages to using small animal, namely rodent, models in xenotransplantation research. For example, the use of the mouse model allows the use of knockout mice and careful dissection of rejection mechanisms at the molecular level. The following models can be used to study hyperacute rejection (HAR): guinea-pig-to-rat, mouse-to-rabbit, guinea-pig-to-mouse, rat-to-presensitised mouse and rat-to-α-Gal knockout mouse. The hamster-to-rat, mouse-to-rat and rat-to-mouse models are commonly used to study acute vascular rejection. Large animal models are complex and expensive, but they are more relevant to clinical xenotransplantation. Based on experiments using transgenic pig-to-primate models, HAR can be overcome. However, acute vascular rejection remains a major barrier at the present time. A pig cartilage-to-monkey model has been developed to study chronic rejection. Other novel models such as pig venous segment-to-monkey model and rat-to-primate model may represent viable options to study immunological barriers following xenotransplantation. Like many other medical breakthroughs, animal research will continue to make enormous contributions towards the eventual success of xenotransplantation.