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Brief Communication
Nature Medicine  11, 29 - 31 (2004)
Published online: 26 December 2004; | doi:10.1038/nm1171

Heart transplantation in baboons using alpha1,3-galactosyltransferase gene-knockout pigs as donors: initial experience

Kenji Kuwaki1, Yau-Lin Tseng1, Frank J M F Dor1, Akira Shimizu2, Stuart L Houser3, Todd M Sanderson1, 2, Courtney J Lancos1, Derek D Prabharasuth1, Jane Cheng2, Kathleen Moran2, Yosuke Hisashi1, Nicolas Mueller4, Kazuhiko Yamada1, Julia L Greenstein2, Robert J Hawley2, Clive Patience2, Michel Awwad2, Jay A Fishman4, Simon C Robson5, Henk-Jan Schuurman2, David H Sachs1 & David K C Cooper1, 6

1  Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, MGH-East, 13th Street, Boston, Massachusetts 02129, USA.

2  Immerge BioTherapeutics Inc., 300 Technology Square, Cambridge, Massachusetts 02139, USA.

3  Department of Pathology, Massachusetts General Hospital/Harvard Medical School, 55 Fruit Street, Boston, Massachusetts 02114, USA.

4  Infectious Disease Division, Massachusetts General Hospital/Harvard Medical School, 55 Fruit Street, Boston, Massachusetts 02114, USA.

5  Center for Immunobiology, Beth Israel Deaconess Medical Center/Harvard Medical School, 99 Brookline Avenue, Boston, Massachusetts 02215, USA.

6  Current address: Starzl Transplantation Institute, University of Pittsburgh Medical Center, Biomedical Sciences Tower East, Room E1550A, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA.

Correspondence should be addressed to David K C Cooper cooperdk@upmc.edu
Hearts from alpha1,3-galactosyltransferase knockout pigs (GalT-KO, n = 8) were transplanted heterotopically into baboons using an anti-CD154 monoclonal antibody−based regimen. The elimination of the galactose-alpha1,3-galactose epitope prevented hyperacute rejection and extended survival of pig hearts in baboons for 2−6 months (median, 78 d); the predominant lesion associated with graft failure was a thrombotic microangiopathy, with resulting ischemic injury. There were no infectious complications directly related to the immunosuppressive regimen. The transplantation of hearts from GalT-KO pigs increased graft survival over previous studies.


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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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