Characterization of porcine complement regulatory molecules. Application toxenotransplantation

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Project objective

Research objectives and content Little is known about the regulation of complement in pigs and the current enthusiasm for using the pig as an organ donor for humans increases the need for an understanding of pig complement. Pigs are currently being engineered to express human complement regulators in the expectation that organs from these pigs will be less susceptible to damage by human complement and will escape hyperacute rejection. However, these experiments have been conducted in relative ignorance of pig complement and of its own regulatory molecules. This project is intended to accomplish a deep characterization of the pig complement regulatory molecules, mainly in the context of the pig to human xenotransplantation. Thus, it is focused in the three cell membrane-bound molecules: MCP (or CD46), CD59 and DAF {or CD55). We will characterise fully the tissue expression of these three molecule and to analyse their roles in vivo. We will address the species selectivity of pig complement regulators. This is, if porcine regulators inhibits the activation of the human complement and the relative efficiency of both systems. These latter questions have obvious relevance to pig-human transplantation. Finally, is intended to carry out several functional analysis of the regulatory capacity of these three molecules. We will assess the relative importance of the proteins in defence against homologous and heterologous complement. Training content (objective, benefit and expected impact) This project will provide new data which will be of value to those engaged in the design of animal organs for transplantation into humans. It will also provide novel information on the regulatory molecules of porcine complement and the possible role of complement regulators in homeostasis, fertility and infection in the pig by virus and parasite. On the other hand, it will contribute to comparative immunology, since it will introduce novel concepts in the evolution of the cornplement system Links with industry / industrial relevance (22) The Spanish industry BioVet-UCO, where the applicant comes from, has expressed a great interest in this project, since it will support partialy this fellowship. The company concentrates on research, development and manufacturing, manufacturing with a technological focus on monoclonal antibodies. BioVet-UCO will pay special attention to swine immunology taking into account the emerging relevance of pigs as organ donors for xenotransplantation. Thus, BioVet-UCO is also interested in the study of the porcine complement regulatory molecules and in the development and characterisation of monoclonal antibodies to these molecules. Transgenic swine would need a special immunological care and BioVet-UCO will offer reagents for immunological control. These reagents could also be applied to the study of xenotransplantation and xenograft rejection.

Original text from CORDIS.

Participants

• UNIVERSITY OF WALES COLLEGE OF MEDICINE · CARDIFFCoordinatorCity levelUnited Kingdom
• Not availableCity levelSpain

Links

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