Comparative physiology and immunology

The aim of this sub-project is to characterize through ex vivo and in vivo studies, the functional response of kidney from control and engineered pigs to the human microenvironment, in particular for vasoactive hormones and for those which regulate the electrolyte and calcium phosphate metabolism and the kidney compensatory responses to changes in dietary sodium intake and in circulating volume expansion, and responses to drugs, especially diuretics.

It is expected to provide information on the kidney of engineered pigs able to maintain homeostasis of volumes, electrolyte and calcium/phosphorus metabolism in an environment which mimics the condition of kidney transplantation in human. The results of these studies will contribute to define the future of the xenotransplantation (transplantation between different species) of pig kidneys in humans.

With regard to the immunology, it is required to characterize the response of human T and B lymphocytes to the antigens of engineered pigs comparing it with the most common response to human allogeneic antigens through in vitro and ex vivo studies. Is also expected to define the immunosuppressive/tollerogenic in vitro response by transfection of the gene coding for the CTLA4Ig protein in cells of engineered pigs.

The possible practical applications refer to the development of procedures able to bring xenotransplantation from the pre-clinical experimental stage to clinical phase. The possible consequences are related to the development of clinical procedures and patents and also to the development of an optimised animal as tissues and organs donor for patients awaiting transplant.

The potential market for this service is not limited on a local level, as it is demonstrated by the fact that the lead partner is already a supplier of cloned pigs for international laboratories working on xenotransplantation.