Immunobiology of liver xenotransplantation.
Pigs are currently the preferred species for future organ xenotransplantation. With advances in the development of genetically modified pigs, clinical xenotransplantation is becoming closer to reality. In preclinical studies (pig-to-nonhuman primate), the xenotransplantation of livers from pigs transgenic for human CD55 or from α1,3-galactosyltransferase gene-knockout pigs+/- transgenic for human CD46, is associated with survival of approximately 7-9 days. Although hepatic function, including coagulation, has proved to be satisfactory, the immediate development of thrombocytopenia is very limiting for pig liver xenotransplantation even as a 'bridge' to allotransplantation. Current studies are directed to understand the immunobiology of platelet activation, aggregation and phagocytosis, in particular the interaction between platelets and liver sinusoidal endothelial cells, hepatocytes and Kupffer cells, toward identifying interventions that may enable clinical application.
Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Burcin
B
Ekser
Christopher
C
Burlak
Joshua P
JP
Waldman
Andrew J
AJ
Lutz
Leela L
LL
Paris
Massimiliano
M
Veroux
Simon C
SC
Robson
Michael A
MA
Rees
David
D
Ayares
Bruno
B
Gridelli
A Joseph
AJ
Tector
David Kc
DK
Cooper
D000818:Animals; D030801:Animals, Genetically Modified; D001792:Blood Platelets / Q000276:immunology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology*; D013552:Swine; D014183:Transplantation, Heterologous / Q000009:adverse effects / Q000276:immunology*