Hyperacute rejection is attenuated in GalT knockout swine lungs perfused ex vivo with human blood

Carsten Schroeder, J. S. Allan, B. N. Nguyen, G. Wu, T. Zhang, A. M. Azimzadeh, J. C. Madsen, H. J. Schuurman, D. H. Sachs, R. N. Pierson

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background. Hyperacute rejection (HAR) is one of the principal obstacles to successful xenotransplantation. Homozygous α-1,3-galactosyltransferase knockout (GalT-KO) miniature swine now offer the prospect of overcoming this barrier to xenotransplantation. In this study, the short-term function of GalT-KO swine lungs was evaluated in a well-established ex vivo model of swine-to-human lung xenotransplantation. Methods. Lungs from homozygous GalT-KO swine (n = 3) and control lungs from pigs of the background strain used to create the GalT-KO pig line (n = 2) were perfused ex vivo with freshly collected heparinized human blood. Graft function was assessed by various physiologic measurements, serial histologic and immunohistochemical evaluation, and assays of complement and platelet activation. Results. Xenoperfused control swine lungs exhibited HAR with graft survival times <5 minutes. In contrast, GalT-KO swine lungs retained their function for approximately 2 hours, on average. GalT-KO swine lungs showed decreased complement and platelet activation compared with controls. Nonetheless, activation of complement and coagulation cascades was not completely eliminated in the GalT-KO swine lungs. Conclusions. The survival of xenoperfused GalT-KO swine lungs was significantly prolonged, as compared with control lungs expressing Gal. This appears to have been due largely to substantially reduced complement activation. Nonetheless, the xenoperfused GalT-KO lungs still showed some evidence of complement fixation and intravascular coagulopathy by the time of graft demise.

Original languageEnglish (US)
Pages (from-to)512-513
Number of pages2
JournalTransplantation Proceedings
Volume37
Issue number1
DOIs
StatePublished - Jan 1 2005
Externally publishedYes

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Galactosyltransferases
Swine
Lung
Complement Activation
Heterologous Transplantation
Platelet Activation
Transplants
Miniature Swine
Graft Survival

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

Schroeder, C., Allan, J. S., Nguyen, B. N., Wu, G., Zhang, T., Azimzadeh, A. M., ... Pierson, R. N. (2005). Hyperacute rejection is attenuated in GalT knockout swine lungs perfused ex vivo with human blood. Transplantation Proceedings, 37(1), 512-513. https://doi.org/10.1016/j.transproceed.2004.12.133

Hyperacute rejection is attenuated in GalT knockout swine lungs perfused ex vivo with human blood. / Schroeder, Carsten; Allan, J. S.; Nguyen, B. N.; Wu, G.; Zhang, T.; Azimzadeh, A. M.; Madsen, J. C.; Schuurman, H. J.; Sachs, D. H.; Pierson, R. N.

In: Transplantation Proceedings, Vol. 37, No. 1, 01.01.2005, p. 512-513.

Research output: Contribution to journalArticle

Schroeder, C, Allan, JS, Nguyen, BN, Wu, G, Zhang, T, Azimzadeh, AM, Madsen, JC, Schuurman, HJ, Sachs, DH & Pierson, RN 2005, 'Hyperacute rejection is attenuated in GalT knockout swine lungs perfused ex vivo with human blood', Transplantation Proceedings, vol. 37, no. 1, pp. 512-513. https://doi.org/10.1016/j.transproceed.2004.12.133
Schroeder, Carsten ; Allan, J. S. ; Nguyen, B. N. ; Wu, G. ; Zhang, T. ; Azimzadeh, A. M. ; Madsen, J. C. ; Schuurman, H. J. ; Sachs, D. H. ; Pierson, R. N. / Hyperacute rejection is attenuated in GalT knockout swine lungs perfused ex vivo with human blood. In: Transplantation Proceedings. 2005 ; Vol. 37, No. 1. pp. 512-513.
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AU - Zhang, T.

AU - Azimzadeh, A. M.

AU - Madsen, J. C.

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AU - Sachs, D. H.

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N2 - Background. Hyperacute rejection (HAR) is one of the principal obstacles to successful xenotransplantation. Homozygous α-1,3-galactosyltransferase knockout (GalT-KO) miniature swine now offer the prospect of overcoming this barrier to xenotransplantation. In this study, the short-term function of GalT-KO swine lungs was evaluated in a well-established ex vivo model of swine-to-human lung xenotransplantation. Methods. Lungs from homozygous GalT-KO swine (n = 3) and control lungs from pigs of the background strain used to create the GalT-KO pig line (n = 2) were perfused ex vivo with freshly collected heparinized human blood. Graft function was assessed by various physiologic measurements, serial histologic and immunohistochemical evaluation, and assays of complement and platelet activation. Results. Xenoperfused control swine lungs exhibited HAR with graft survival times <5 minutes. In contrast, GalT-KO swine lungs retained their function for approximately 2 hours, on average. GalT-KO swine lungs showed decreased complement and platelet activation compared with controls. Nonetheless, activation of complement and coagulation cascades was not completely eliminated in the GalT-KO swine lungs. Conclusions. The survival of xenoperfused GalT-KO swine lungs was significantly prolonged, as compared with control lungs expressing Gal. This appears to have been due largely to substantially reduced complement activation. Nonetheless, the xenoperfused GalT-KO lungs still showed some evidence of complement fixation and intravascular coagulopathy by the time of graft demise.

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