Transgenic expression in pig hearts of both human decay-accelerating factor and human membrane cofactor protein does not provide an additional benefit to that of human decay-accelerating factor alone in pig-to-baboon xenotransplantation.
This study investigated whether the coexpression of human decay-accelerating factor (hDAF) and human membrane cofactor protein (hMCP) on porcine organs provides an additional benefit to that of hDAF alone to prevent rejection. Heterotopic heart xenotransplantation was performed in baboons with either hDAF (n=5) or hDAF/hMCP (n=5) transgenic pig organs. The only immunosuppression given was GAS914 (a soluble Gal [alpha1-3] Gal polymer) and cyclosporine A. With the exception of one hDAF organ that failed from a left atrium thrombosis, all xenografts developed acute humoral xenograft rejection. Acute humor xenograft rejection occurred at a median time of 152 hr in hDAF hearts and 162 hr in hDAF/hMCP organs. Recipients of hDAF or hDAF/hMCP hearts did not differ in their patterns of serum antiporcine antibodies or in plasma levels of the soluble terminal complement complex sC5b-9. It is concluded that in this pig-to-baboon heterotopic heart transplant, model expression of hDAF/hMCP does not provide an additional benefit in prevention of rejection to that of hDAF alone.
Mañez
Rafael
R
Transplantation Division, Complejo Hospitalario Universitario Juan Canalejo, La Coruña, Spain. rmanez@csub.scs.es
Lopez-Pelaez
Eduardo
E
Centeno
Alberto
A
Herrera
Jose M
JM
Juffe
Alberto
A
Domenech
Nieves
N
Harrison
Richard
R
Schuurman
Henk-Jan
HJ
D000818:Animals; D030801:Animals, Genetically Modified; D015703:Antigens, CD / Q000235:genetics*; D018958:CD55 Antigens / Q000235:genetics*; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000235:genetics*; D010215:Papio; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000276:immunology*; D014312:Trisaccharides / Q000627:therapeutic use
D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D007166:Immunosuppressive Agents; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D014312:Trisaccharides; C076569:alpha-galactosyl epitope; D016572:Cyclosporine