[Transgenic swine as potential organ donors? Results of the ex-vivo hemoperfusion hDAF transgenic kidney with human blood].
Kidney xenotransplantation is not yet a realistic clinical treatment modality. However, during the last decades more than 30 kidneys from other species have been transplanted into humans; some of the kidneys sustained some function up to 60 days. Recent progress in genetic engineering has raised the possibility to create large transgenic animals which express human complement regulatory proteins (CRP). Since early complement activation is believed to be the main triggering event for xenograft destruction, complement regulation by species-specific CRP should avoid hyperacute rejection in transspecies transplantation. The perfusion of hDAF-transgenic pig kidneys with human blood was not associated with the morphological signs of hyperacute rejection when compared to non-transgenic control organs. Specific immunohistology could demonstrate that the transgene was sufficient to regulate complement activation beyond C3 despite the endothelial deposition of xenoantibodies. In the future, these organs could be further optimized and ultimately tested in a clinical pilot protocol under appropriate immunosuppression.
Storck
M
M
Abt. Thorax- und Gefässchirurgie, Universität Ulm.
Abendroth
D
D
White
D J
DJ
Pino-Chavez
G
G
Fakler
J A
JA
Hammer
C
C
D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics*; D018958:CD55 Antigens / Q000235:genetics*; D003167:Complement Activation / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000502:physiology; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D009926:Organ Preservation / Q000295:instrumentation*; D010477:Perfusion / Q000295:instrumentation*; D013552:Swine / Q000235:genetics*; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000473:pathology
D018958:CD55 Antigens