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Islet xenotransplantation using gal-deficient neonatal donors improves engraftment and function

Publication ,  Journal Article
Thompson, P; Badell, IR; Lowe, M; Cano, J; Song, M; Leopardi, F; Avila, J; Ruhil, R; Strobert, E; et al.,
Published in: American Journal of Transplantation
2011

Significant deficiencies in understanding of xenospecific immunity have impeded the success of preclinical trials in xenoislet transplantation. Although galactose-α1,3-galactose, the gal epitope, has emerged as the principal target of rejection in pig-to-primate models of solid organ transplant, the importance of gal-specific immunity in islet xenotransplant models has yet to be clearly demonstrated. Here, we directly compare the immunogenicity, survival and function of neonatal porcine islets (NPIs) from gal-expressing wild-type (WT) or gal-deficient galactosyl transferase knockout (GTKO) donors. Paired diabetic rhesus macaques were transplanted with either WT (n = 5) or GTKO (n = 5) NPIs. Recipient blood glucose, transaminase and serum xenoantibody levels were used to monitor response to transplant. Four of five GTKO versus one of five WT recipients achieved insulin-independent normoglycemia; transplantation of WT islets resulted in significantly greater transaminitis. The WT NPIs were more susceptible to antibody and complement binding and destruction in vitro. Our results confirm that gal is an important variable in xenoislet transplantation. The GTKO NPI recipients have improved rates of normoglycemia, likely due to decreased susceptibility of xenografts to innate immunity mediated by complement and preformed xenoantibody. Therefore, the use of GTKO donors is an important step toward improved consistency and interpretability of results in future xenoislet studies. © Copyright 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

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Published In

American Journal of Transplantation

DOI

ISSN

1600-6135

Publication Date

2011

Volume

11

Issue

12

Start / End Page

2593 / 2602

Related Subject Headings

  • Transplantation, Heterologous
  • Tissue Donors
  • Swine
  • Surgery
  • Macaca mulatta
  • Islets of Langerhans Transplantation
  • Immunoenzyme Techniques
  • Immunity, Innate
  • Graft Rejection
  • Galactosyltransferases
 

Citation

APA
Chicago
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MLA
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Thompson, P., Badell, I. R., Lowe, M., Cano, J., Song, M., Leopardi, F., … et al., . (2011). Islet xenotransplantation using gal-deficient neonatal donors improves engraftment and function. American Journal of Transplantation, 11(12), 2593–2602. https://doi.org/10.1111/j.1600-6143.2011.03720.x
Thompson, P., I. R. Badell, M. Lowe, J. Cano, M. Song, F. Leopardi, J. Avila, R. Ruhil, E. Strobert, and E. et al. “Islet xenotransplantation using gal-deficient neonatal donors improves engraftment and function.” American Journal of Transplantation 11, no. 12 (2011): 2593–2602. https://doi.org/10.1111/j.1600-6143.2011.03720.x.
Thompson P, Badell IR, Lowe M, Cano J, Song M, Leopardi F, et al. Islet xenotransplantation using gal-deficient neonatal donors improves engraftment and function. American Journal of Transplantation. 2011;11(12):2593–602.
Thompson, P., et al. “Islet xenotransplantation using gal-deficient neonatal donors improves engraftment and function.” American Journal of Transplantation, vol. 11, no. 12, 2011, pp. 2593–602. Manual, doi:10.1111/j.1600-6143.2011.03720.x.
Thompson P, Badell IR, Lowe M, Cano J, Song M, Leopardi F, Avila J, Ruhil R, Strobert E, et al. Islet xenotransplantation using gal-deficient neonatal donors improves engraftment and function. American Journal of Transplantation. 2011;11(12):2593–2602.
Journal cover image

Published In

American Journal of Transplantation

DOI

ISSN

1600-6135

Publication Date

2011

Volume

11

Issue

12

Start / End Page

2593 / 2602

Related Subject Headings

  • Transplantation, Heterologous
  • Tissue Donors
  • Swine
  • Surgery
  • Macaca mulatta
  • Islets of Langerhans Transplantation
  • Immunoenzyme Techniques
  • Immunity, Innate
  • Graft Rejection
  • Galactosyltransferases