title: The role of genetically engineered pigs in xenotransplantation research.
abstract: There is a critical shortage in the number of deceased human organs that become available for the purposes of clinical transplantation. This problem might be resolved by the transplantation of organs from pigs genetically engineered to protect them from the human immune response. The pathobiological barriers to successful pig organ transplantation in primates include activation of the innate and adaptive immune systems, coagulation dysregulation and inflammation. Genetic engineering of the pig as an organ source has increased the survival of the transplanted pig heart, kidney, islet and corneal graft in non-human primates (NHPs) from minutes to months or occasionally years. Genetic engineering may also contribute to any physiological barriers that might be identified, as well as to reducing the risks of transfer of a potentially infectious micro-organism with the organ. There are now an estimated 40 or more genetic alterations that have been carried out in pigs, with some pigs expressing five or six manipulations. With the new technology now available, it will become increasingly common for a pig to express even more genetic manipulations, and these could be tested in the pig-to-NHP models to assess their efficacy and benefit. It is therefore likely that clinical trials of pig kidney, heart and islet transplantation will become feasible in the near future.
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, PA, USA.
authors.forename: David K C
authors.initials: DK
authors.lastname: Cooper
authors.affiliation: Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Burcin
authors.initials: B
authors.lastname: Ekser
authors.affiliation: Revivicor, Blacksburg, VA, USA.
authors.forename: Jagdeece
authors.initials: J
authors.lastname: Ramsoondar
authors.affiliation: Revivicor, Blacksburg, VA, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Phelps
authors.affiliation: Revivicor, Blacksburg, VA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Ayares
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics / Q000276:immunology; D000818:Animals; D030801:Animals, Genetically Modified; D000941:Antigens / Q000378:metabolism; D035843:Biomedical Research / Q000379:methods; D001778:Blood Coagulation Disorders / Q000517:prevention & control; D002986:Clinical Trials as Topic; D003165:Complement System Proteins / Q000235:genetics / Q000276:immunology; D004187:Disaccharides / Q000276:immunology; D005818:Genetic Engineering / Q000379:methods*; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D061214:Patient Safety; D011323:Primates; D013552:Swine / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology; D009927:Tissue and Organ Procurement / Q000379:methods; D014181:Transplantation Immunology / Q000502:physiology; D014183:Transplantation, Heterologous / Q000379:methods*
chemical_list: D000941:Antigens; D004187:Disaccharides; C055075:galactosyl-(1-3)galactose; D003165:Complement System Proteins
keywords: genetically-engineered; islets; non-human primate; organs; pig; xenotransplantation