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Related Experiment Videos

Transgenic human decay accelerating factor makes normal pigs function as a concordant species

M Schmoeckel1, G Nollert, M Shahmohammadi

  • 1Department of Cardiac Surgery, Klinikum Grosshadern, University of Munich, Germany.

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
|July 1, 1997
PubMed
Summary

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Transgenic human decay accelerating factor (DAF) in pig hearts significantly reduced hyperacute rejection in xenotransplantation. This prevents endothelial cell damage and myocardial injury, making pig organs viable for transplantation.

Area of Science:

  • Xenotransplantation research
  • Immunology
  • Cardiovascular surgery

Background:

  • Xenotransplantation offers a solution to organ shortages.
  • Hyperacute rejection is a major barrier in xenotransplantation.
  • Transgenic pigs expressing human decay accelerating factor (DAF) were developed to mitigate rejection.

Purpose of the Study:

  • To evaluate the efficacy of human DAF in preventing hyperacute rejection.
  • To assess the hemodynamic performance of DAF-transgenic pig hearts.
  • To compare DAF-transgenic pig hearts with non-transgenic pig hearts and rhesus monkey hearts.

Main Methods:

  • An ex vivo working heart model was utilized.
  • Hemodynamic performance was compared across three groups: DAF-transgenic pig hearts, Landrace pig hearts, and rhesus monkey hearts.

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  • Biochemical markers of endothelial activation and myocardial damage were analyzed from coronary sinus effluent.

    • Main Results:

    • DAF-transgenic pig hearts (Group A) and rhesus monkey hearts (Group C) demonstrated superior cardiac performance (Stroke Work Index) compared to Landrace pig hearts (Group B).
    • Group B exhibited significantly higher levels of endothelial activation markers (6-keto prostaglandin F1 alpha, prostaglandin E2) and myocardial damage markers (creatine phosphokinase, lactate dehydrogenase) than Groups A and C.
    • Histological analysis revealed single-cell necrosis in Group B, contrasting with interstitial edema in Groups A and C.

    Conclusions:

    • Human DAF plays a critical role in preventing hyperacute rejection in discordant xenotransplantation.
    • Transgenic human DAF effectively inhibits complement-mediated endothelial cell damage.
    • This inhibition prevents endothelial activation and subsequent myocardial damage, enabling pig organs to function as if from a concordant species.