FOR 535:  Xenotransplantation

• Subject Area: Medicine
• Term: from 2004 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5470814

Transplantation of porcine xenografts into human recipients is a realistic option to overcome the growing worldwide shortage of suitable allogeneic organs. Nowadays, the hyperacute rejection response (HAR) induced by a porcine organ can reliably be overcome by expression of human complement regulating proteins and/or ablation of a-gal-epitopes in pigs, and the risk of a potential transmission of pathogens is consi-dered minimal.
The strategy of this consortium is to generate multi-transgenic pigs which control HAR, the coagulation disorder and the delayed rejection. These animals will be characterised in detail, the biological effects of the transgenes and the physiological compatibility will be determined by novel "in vitro" models, "ex vivo" perfusion systems for kidneys and hearts and transplantation into primates; viral safety of the porcine organs will be assessed in parallel.
The consortium is unique as it assembles a true interdisciplinary group of leading German laboratories inclusive animal biotechnologists, immunologists, transplantation surgeons and virologists. Results will make a significant and original contribution towards international xenotransplantation research and will advance xenotransplantation up to preclinical testing.

• DFG Programme: Research Units

Projects

• Central project (Public relations and secretary) (Applicant Reichart, Bruno )
• Improved multi-transgenic pig lines for xenotransplantation (Applicant Niemann, Heiner )
• Modifying consumptive coagulopathy following discordant porcine xenotransplantation - In vitro and in vivo analysis of enhanced HO-I expression on native and modified porcine cells and kidneys (Applicant Winkler, Michael )
• Modulation of xenogeneic responses via regulatory T cells (Applicant Schendel, Ph.D., Dolores J. )
• Multitransgenic donor animals and new immunosuppressive strategies in preclinical experimental xenotransplantation models (Applicant Brenner, Paolo )
• Porcine endogenous retroviruses (PERVs) and xenotransplantation: Safety evaluation, diagnostics and inhibition by siRNA (Applicant Tönjes, Ralf R. )
• Porcine endogenous retroviruses (PERVs) and xenotransplantation: Safety evaluation, diagnostics and inhibition by siRNA (Applicant Denner, Joachim )
• Recombinant adeno-associated virus-mediated transgene delivery into porcine organs to allow immunological modifications of xenografts (Applicant Hallek, Michael )
• Sus artificial chromosomes (SusACs) for the stable segregation of multiple transgenes (Applicant Schindelhauer, Dirk )
• Targeting of costimulatory signaling pathways for the control of human anti-pig cellular immune responses (Applicant Schwinzer, Reinhard )
• Transgenic strategies to overcome cellular rejection of pig-to-primate xenografts (Applicants Seissler, Jochen ;  Wolf, Eckhard )
• Viral strategies for xenotransplantation (Applicant Kupatt, Christian )

• Spokesperson: Professor Dr. Bruno Reichart