title: Potential of aspirin to inhibit thrombotic microangiopathy in alpha1,3-galactosyltransferase gene-knockout pig hearts after transplantation in baboons.
abstract: Hearts from alpha1,3-Galactosyltransferase gene-knockout (GaIT-KO) pigs were transplanted heterotopically into 8 baboons that received an anti-CD154 monoclonal antibody (mAb)-based immunosuppressive regimen and heparin. Three baboons died or were euthanized with beating grafts on 16, 23, and 56 days, respectively, and the remaining 5 grafts functioned for 59-179 days. Hyperacute rejection did not occur, and classical features of acute humoral xenograft or acute cellular rejection were rare. However, thrombotic microangiopathy (TM) developed in all cases; its onset was delayed in 2 baboons that received aspirin. Function of a pig organ in a baboon for a period approaching 6 months has not been reported previously and lends encouragement that the barriers to xenotransplantation will be overcome, but TM requires investigation.
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: F J M F
authors.initials: FJ
authors.lastname: Dor
authors.forename: K
authors.initials: K
authors.lastname: Kuwaki
authors.forename: Y-L
authors.initials: YL
authors.lastname: Tseng
authors.forename: A
authors.initials: A
authors.lastname: Shimizu
authors.forename: S L
authors.initials: SL
authors.lastname: Houser
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: R J
authors.initials: RJ
authors.lastname: Hawley
authors.forename: C
authors.initials: C
authors.lastname: Patience
authors.forename: M
authors.initials: M
authors.lastname: Awwad
authors.forename: J A
authors.initials: JA
authors.lastname: Fishman
authors.forename: S C
authors.initials: SC
authors.lastname: Robson
authors.forename: D H
authors.initials: DH
authors.lastname: Sachs
authors.forename: H-J
authors.initials: HJ
authors.lastname: Schuurman
authors.forename: D K C
authors.initials: DK
authors.lastname: Cooper
mesh_terms: D000818:Animals; D001241:Aspirin / Q000627:therapeutic use*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005700:Galactosyltransferases / Q000172:deficiency* / Q000235:genetics*; D017353:Gene Deletion; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D016027:Heart Transplantation / Q000379:methods*; D010215:Papio; D013552:Swine; D013927:Thrombosis / Q000517:prevention & control*; D014183:Transplantation, Heterologous / Q000379:methods*
chemical_list: D005343:Fibrinolytic Agents; D005700:Galactosyltransferases; C037959:beta-D-galactosyl-N-acetylglucosaminylglycopeptide alpha-1,3-galactosyltransferase; D001241:Aspirin