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POTENTIAL USE OF GENETICALLY MODIFIED PIGS AS ORGAN DONORS FOR TRANSPLANTATION INTO HUMANS
Author(s) -
Logan John S,
Sharma Ajay
Publication year - 1999
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.1999.03185.x
Subject(s) - xenotransplantation , economic shortage , transplantation , transgene , genetically modified organism , complement system , biology , genetically modified mouse , immunology , allotransplantation , organ donation , medicine , antibody , genetics , gene , linguistics , philosophy , government (linguistics)
SUMMARY 1. Transplantation is currently viewed as a successful treatment for end‐stage organ failure. Its more widespread use is severely limited by a shortage of human organ donors. This has stimulated the scientific and medical communities to look at the potential use of animals to solve this problem. For a number of reasons, the pig appears to be the preferred species. 2. The initial immunological problem encountered in pig‐to‐primate transplantation is a process of hyperacute rejection, which is mediated by the binding of antibodies to the graft endothelium followed by the activation of the complement cascade. We have sought to overcome these initial immunological challenges by focusing our attention not only on the recipient of the graft but also on the donor. Therefore, we have generated transgenic animals with specific genetic modifications designed to inhibit the activation of the complement cascade. Upon transplantation to baboons of organs derived from these transgenic pigs, we have been able to demonstrate that hyperacute rejection can be prevented. We will discuss the generation of these and other transgenic animals and their potential role in clinical xenotransplantation.