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Heart transplantation in baboons using α1,3-galactosyltransferase gene-knockout pigs as donors: initial experience

Nature Medicine volume 11, pages 29–31 (2005)Cite this article

Abstract

Hearts from α1,3-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-α1,3-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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Figure 1: Representative histopathology and immunofluorescence of GaIT-KO pig heart grafts.

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Acknowledgements

We thank L. Buhler and C. Knosalla for their comments on this manuscript, and R. Colvin for comments on the histopathology. We also thank W. Schuler and his colleagues at the Novartis Institutes for Biomedical Research for making ABI793 available to us, and P. Albientz, R. Buergi and F. Legay for developing the assay to measure levels of ABI793. Y-L Tseng is a recipient of a grant from the National Cheng Kung University Hospital, Taiwan. F.J.M.F. Dor is a recipient of grants from the Ter Meulen Fund from the Royal Netherlands Academy of Arts and Sciences, the Prof. Michaël-van Vloten Fund, and the Netherland-America Foundation. D.H. Sachs, J.A. Fishman, S.C. Robson, K. Yamada and D.K.C. Cooper were consultants to Immerge BioTherapeutics, Inc. This work was supported in part by US National Institutes of Health Program Project 1PO1A45897 and by a Sponsored Research Agreement between the Massachusetts General Hospital and Immerge BioTherapeutics, Inc.

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Author notes

  1. David K C Cooper

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

Authors and Affiliations

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

    Kenji Kuwaki, Yau-Lin Tseng, Frank J M F Dor, Todd M Sanderson, Courtney J Lancos, Derek D Prabharasuth, Yosuke Hisashi, Kazuhiko Yamada, David H Sachs & David K C Cooper

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

    Akira Shimizu, Todd M Sanderson, Jane Cheng, Kathleen Moran, Julia L Greenstein, Robert J Hawley, Clive Patience, Michel Awwad & Henk-Jan Schuurman

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

    Stuart L Houser

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

    Nicolas Mueller & Jay A Fishman

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

    Simon C Robson

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Corresponding author

Correspondence to David K C Cooper.

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Competing interests

The following authors were employees at Immerge BioTherapeutics, Inc. at the time of the study: Akira Shimizu, Todd M. Sanderson, Jan Cheng, Kathleen Moran, Julia L. Greenstein, Robert J. Hawley, Clive Patience, Michel Awwad, and Henk-Jen Schuurman.

The following authors were consultants of Immerge BioTherapeutics Inc. at the time of the study: David H. Sachs, Jay A. Fishman, Simon C. Robson, Kazuhiko Yamada, and David K.C. Cooper.

Supplementary information

Supplementary Fig. 1

T cell (a) and B cell (b) counts until the time of excision of the graft in the baboons of Group 1. (PDF 105 kb)

Supplementary Fig. 2

Levels of anti-Gal IgM (a) and IgG (b) reactive with Gal type 6 during first 120 days or until the time of excision of the graft. (PDF 75 kb)

Supplementary Fig. 3

Representative mixed lymphocyte reactions, performed as reported previously22 (pre-transplantation, and on days 28, 70, 119 and 153) in B223, which underwent graftectomy and discontinuation of immunosuppressive therapy on day 110. (PDF 75 kb)

Supplementary Methods (PDF 133 kb)

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Kuwaki, K., Tseng, YL., Dor, F. et al. Heart transplantation in baboons using α1,3-galactosyltransferase gene-knockout pigs as donors: initial experience. Nat Med 11, 29–31 (2005). https://doi.org/10.1038/nm1171

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