Potential of aspirin to inhibit thrombotic microangiopathy in alpha1,3-galactosyltransferase gene-knockout pig hearts after transplantation in baboons.
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.
Dor
F J M F
FJ
Transplantation Biology Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
Kuwaki
K
K
Tseng
Y-L
YL
Shimizu
A
A
Houser
S L
SL
Yamada
K
K
Hawley
R J
RJ
Patience
C
C
Awwad
M
M
Fishman
J A
JA
Robson
S C
SC
Sachs
D H
DH
Schuurman
H-J
HJ
Cooper
D K C
DK
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*
D005343:Fibrinolytic Agents; D005700:Galactosyltransferases; C037959:beta-D-galactosyl-N-acetylglucosaminylglycopeptide alpha-1,3-galactosyltransferase; D001241:Aspirin