Refinement of a transplantation project in the non-human primate by the use of a humane endpoint.

An assessment scheme was developed to establish a humane endpoint in a pig-to-primate renal xenotransplantation project, with a view to minimizing and controlling any pain or suffering conditions in the animals involved while still achieving the scientific objective. In particular, the assessment criteria for identifying the earliest endpoint are described, bearing in mind both the researcher's need to obtain top-quality data and the ethical need to safeguard the animals. The scheme should also be applicable to other experiments involving non-human primates (e.g. allotransplantation, survival after major surgery, pharmacological safety tests) because it considers reproducible general parameters together with aspects specific to each experimental model.

An update on xenotransplantation.

Xenotransplantation is one of the possible avenues currently being explored to address the shortage problem of human organs. With this in mind, this article will briefly review the current situation with respect to the immunological, physiological and biosafety aspects related to the transplantation of pig organs into primates. Acute humoral xenograft rejection (AHXR) currently remains the central immunological obstacle and the development of strategies for both a better control of the elicited anti-pig humoral immune response or the prevention of the onset of coagulation disorders that accompany AHXR are the two primary focuses of research. To date, porcine xenografts have been shown to sustain the life of nonhuman primates for several months. Such preclinical studies have also demonstrated the absence of insurmountable physiological incompatibilities between pig and primate. In addition, reassuring findings regarding biosafety aspects have been generated and pro-active research aimed at the identification of an organ source with a higher safety profile is also underway. These advancements, in conjunction with ongoing research in pig genetic engineering, immunosuppression and tolerance are expected to further extend the survival of porcine xenografts transplanted into primates. However, until further physiological, efficacy and safety data are generated in relevant primate models, clinical xenotransplantation should not be considered.