Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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

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.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Representative histopathology and immunofluorescence of GaIT-KO pig heart grafts.

References

  1. Good, A.H. et al. Transplant Proc. 24, 559–562 (1992).

    CAS  PubMed  Google Scholar 

  2. Cooper, D.K.C. Clin. Transplantation 6, 178–183 (1992).

    CAS  Google Scholar 

  3. Oriol, R., Ye, Y., Koren, E. & Cooper, D.K.C. Transplantation 56, 1433–1442 (1993).

    Article  CAS  Google Scholar 

  4. Lin, S. et al. Transplantation 70, 1667–1674 (2000).

    Article  CAS  Google Scholar 

  5. Cooper, D.K.C., Koren, E. & Oriol, R. Lancet 342, 682–683 (1993).

    Article  CAS  Google Scholar 

  6. Phelps, C.J. et al. Science 299, 411–414 (2003).

    Article  CAS  Google Scholar 

  7. Kolber-Simonds, D. et al. Proc. Natl. Acad. Sci. USA 19, 7335–7340 (2004).

    Article  Google Scholar 

  8. Dor, F.J.M.F. et al. Transplantation 78, 15–20 (2004).

    Article  CAS  Google Scholar 

  9. Kuwaki, K. et al. Am. J. Transplant. 4, 363–372 (2004).

    Article  CAS  Google Scholar 

  10. Teranishi, K., Manez, R., Awwad, M. & Cooper, D.K.C. Xenotransplantation 9, 148–154 (2002).

    Article  Google Scholar 

  11. Robson, S.C., Cooper, D.K.C. & d'Apice, A.J.F. Xenotransplantation. 7 166–176 (2000).

    Article  CAS  Google Scholar 

  12. Kawai, T., Andrews, D., Colvin, R.B., Sachs, D.H. & Cosimi, A.B. Nat. Med. 6, 114 (2000).

    Article  CAS  Google Scholar 

  13. Knosalla, C., Gollackner, B. & Cooper, D.K.C. Transplantation 74, 416–417 (2002).

    Article  Google Scholar 

  14. Mueller, N. et al. J. Virol. 76, 4734–4740 (2002).

    Article  CAS  Google Scholar 

  15. Bühler, L. et al. Transplantation 72, 1743–1752 (2001).

    Article  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David K C Cooper.

Ethics declarations

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)

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm1171

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing