alpha1,3-Galactosyltransferase gene-knockout pig heart transplantation in baboons with survival approaching 6 months.
BACKGROUND
The recent generation of alpha1,3-galactosyltransferase gene-knockout (GalT-KO) pigs has allowed investigation of the survival of GalT-KO pig organs in nonhuman primates.


METHODS
Heterotopic heart transplantation from GalT-KO pigs was carried out in baboons (n=8) using a human antihuman CD154 monoclonal antibody-based immunosuppressive regimen.


RESULTS
In six of the eight cases, graft survival extended to between approximately 2 and 6 months. All grafts developed thrombotic microangiopathy (TM). In particular, the clinical course of one baboon in which the graft functioned for 179 days is summarized. This baboon received aspirin (40 mg on alternate days) from day 4 in addition to heparin, which may have been a factor in the delay of onset and progression of TM and in prolonged graft survival. Maintenance therapy with anti-CD154 mAb, mycophenolate mofetil, and methylprednisolone was associated with persistently low numbers of CD3CD4 and CD3CD8 cells. Despite persisting depletion of these cells, no infectious complications occurred.


CONCLUSIONS
It remains to be established whether TM is related to a very low level of natural preformed or T-cell-induced antibody deposition on the graft, inducing endothelial activation and injury, or to molecular incompatibilities in the coagulation mechanisms between pig and baboon, or to both. However, function of a pig organ in a baboon for a period approaching six months, which has not been reported previously, lends encouragement that the barriers to xenotransplantation will eventually be overcome.
Tseng
Yau-Lin
YL
Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
Kuwaki
Kenji
K
Dor
Frank J M F
FJ
Shimizu
Akira
A
Houser
Stuart
S
Hisashi
Yosuke
Y
Yamada
Kazuhiko
K
Robson
Simon C
SC
Awwad
Michel
M
Schuurman
Henk-Jan
HJ
Sachs
David H
DH
Cooper
David K C
DK
D000818:Animals; D005700:Galactosyltransferases / Q000172:deficiency* / Q000235:genetics* / Q000276:immunology; D006085:Graft Survival; D016027:Heart Transplantation / Q000379:methods* / Q000473:pathology; D008833:Microcirculation / Q000473:pathology; D010215:Papio; D013552:Swine; D013556:Swine, Miniature; D013927:Thrombosis / Q000209:etiology / Q000473:pathology; D014183:Transplantation, Heterologous / Q000379:methods*
D005700:Galactosyltransferases; C037959:beta-D-galactosyl-N-acetylglucosaminylglycopeptide alpha-1,3-galactosyltransferase