title: alpha1,3-Galactosyltransferase gene-knockout pig heart transplantation in baboons with survival approaching 6 months.
abstract: 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.
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: Yau-Lin
authors.initials: YL
authors.lastname: Tseng
authors.forename: Kenji
authors.initials: K
authors.lastname: Kuwaki
authors.forename: Frank J M F
authors.initials: FJ
authors.lastname: Dor
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Stuart
authors.initials: S
authors.lastname: Houser
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Hisashi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamada
authors.forename: Simon C
authors.initials: SC
authors.lastname: Robson
authors.forename: Michel
authors.initials: M
authors.lastname: Awwad
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Schuurman
authors.forename: David H
authors.initials: DH
authors.lastname: Sachs
authors.forename: David K C
authors.initials: DK
authors.lastname: Cooper
mesh_terms: 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*
chemical_list: D005700:Galactosyltransferases; C037959:beta-D-galactosyl-N-acetylglucosaminylglycopeptide alpha-1,3-galactosyltransferase