α1,3-galactosyltransferase gene-knockout pig heart transplantation in baboons with survival approaching 6 months

Yau Lin Tseng, Kenji Kuwaki, Frank J.M.F. Dor, Akira Shimizu, Stuart Houser, Yosuke Hisashi, Kazuhiko Yamada, Simon C. Robson, Michel Awwad, Henk Jan Schuurman, David H. Sachs, David K.C. Cooper

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153 Citations (Scopus)

Abstract

Background. The recent generation of α1,3-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 CD3+CD4+ and CD3+CD8+ 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.

Original languageEnglish
Pages (from-to)1493-1500
Number of pages8
JournalTransplantation
Volume80
Issue number10
DOIs
Publication statusPublished - 2005 Nov

All Science Journal Classification (ASJC) codes

  • Transplantation

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