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Marked prolongation of porcine renal xenograft survival in baboons through the use of α1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue

Nature Medicine volume 11, pages 32–34 (2005)Cite this article

Abstract

The use of animal organs could potentially alleviate the critical worldwide shortage of donor organs for clinical transplantation. Because of the strong immune response to xenografts, success will probably depend upon new strategies of immune suppression and induction of tolerance. Here we report our initial results using α-1,3-galactosyltransferase knockout (GalT-KO) donors and a tolerance induction approach. We have achieved life-supporting pig-to-baboon renal xenograft survivals of up to 83 d with normal creatinine levels.

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Figure 1: Results of GalT-KO renal transplantation.

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Acknowledgements

The authors wish to thank I. McMorrow for her review of the manuscript, S. Arn for herd management and quality control and M. Doherty, E. Samelson-Jones and B. Wong for help in manuscript preparation. D.H. Sachs, A. Shimizu, J. Fishman, D.K. Cooper and K. Yamada were consultants to Immerge Biotherapeutics, Inc. This work was supported in part by the US National Institutes of Health Program Project 1P01A45897 and by a Sponsored Research Agreement between the Massachusetts General hospital and Immerge Biotherapeutics, Inc.

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Authors and Affiliations

  1. Transplantation Biology Research Center, Massachusetts General Hospital, Boston, 02129, Massachusetts, USA

    Kazuhiko Yamada, Koji Yazawa, Akira Shimizu, Takehiro Iwanaga, Yosuke Hisashi, Matthew Nuhn, Patricia O'Malley, Shuji Nobori, Parsia A Vagefi, David K C Cooper, Megan Sykes & David H Sachs

  2. Immerge BioTherapeutics, Cambridge, 02139, Massachusetts, USA

    Clive Patience, Robert J Hawley, Julia Greenstein, Henk-Jan Schuurman & Michel Awwad

  3. Infectious Disease Unit, Massachusetts General Hospital, Boston, 02129, Massachusetts, USA

    Jay Fishman

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  1. Kazuhiko Yamada
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Corresponding author

Correspondence to David H Sachs.

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Competing interests

The following authors were employees of Immerge BioTherapeutics Inc. at the time of the study: Clive Patience, Robert J. Hawley, Julia Greenstein, Henk-Jen Shuurman and Michele Awwad.

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

Supplementary information

Supplementary Fig. 1

Histology of representative vascularized thymic grafts: B113 on day 68. (PDF 179 kb)

Supplementary Fig. 2

Complement-mediated cytotoxicity of anti-non-Gal antibodies before xenotransplantation and on the day of death. (PDF 54 kb)

Supplementary Methods (PDF 32 kb)

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Yamada, K., Yazawa, K., Shimizu, A. et al. Marked prolongation of porcine renal xenograft survival in baboons through the use of α1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue. Nat Med 11, 32–34 (2005). https://doi.org/10.1038/nm1172

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