Xenotransplantation

Christopher Y. Lu, Tarik A. Khair-El-Din, Ingemar A. Dawidson, Thomas M. Butler, Kathleen M. Brasky, Miguel A. Vazquez, Stanley C. Sicher

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Transplantation of solid organs (heart, lung, liver, and kidney) from swine to humans would solve the current critical shortage of cadaver organs needed by patients with end-stage disease of these organs. In addition, transplantation between distant species (discordant xenografting) will require an understanding of a number of unique immunologic features. Discordant xenografts are rejected within minutes to hours after transplantation. This rejection is due to natural immunity by recipients never before exposed to the xenografts. In some species combinations, this fulminant rejection is due to naturally occurring pre-existing antibodies against the xenograft endothelium. In other species combinations, the xenograft activates the alternative pathway of complement. The swine to human species combination is the most clinically relevant. In this combination, natural human and private antibodies recognize alpha-galactosyl residues of glycoproteins and glycolipids. Potential future therapeutic measures to prevent natural immunity include the genetic engineering of human complement inhibitors into swine cell membranes or genetic 'knock out' of the enzymes responsible for placing alpha-galactosyl residues on swine cell surfaces. There are also special considerations in acquired immunity against xenografts. Cytokines and adhesion molecules may not work across species lines. Xenograft antigens may have to be processed by host antigen-presenting cells in order to effectively stimulate the immune system.

Original languageEnglish (US)
Pages (from-to)1122-1130
Number of pages9
JournalFASEB Journal
Volume8
Issue number14
StatePublished - 1994

Fingerprint

xenotransplantation
Heterologous Transplantation
Heterografts
swine
Swine
complement
Complement Inactivating Agents
Innate Immunity
antibodies
antigen-presenting cells
glycolipids
Transplantation
endothelium
genetic engineering
Alternative Complement Pathway
adhesion
cell membranes
immune system
Genetic engineering
glycoproteins

Keywords

  • complement
  • natural antibody
  • primate
  • swine
  • transplantation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Lu, C. Y., Khair-El-Din, T. A., Dawidson, I. A., Butler, T. M., Brasky, K. M., Vazquez, M. A., & Sicher, S. C. (1994). Xenotransplantation. FASEB Journal, 8(14), 1122-1130.

Xenotransplantation. / Lu, Christopher Y.; Khair-El-Din, Tarik A.; Dawidson, Ingemar A.; Butler, Thomas M.; Brasky, Kathleen M.; Vazquez, Miguel A.; Sicher, Stanley C.

In: FASEB Journal, Vol. 8, No. 14, 1994, p. 1122-1130.

Research output: Contribution to journalArticle

Lu, CY, Khair-El-Din, TA, Dawidson, IA, Butler, TM, Brasky, KM, Vazquez, MA & Sicher, SC 1994, 'Xenotransplantation', FASEB Journal, vol. 8, no. 14, pp. 1122-1130.
Lu CY, Khair-El-Din TA, Dawidson IA, Butler TM, Brasky KM, Vazquez MA et al. Xenotransplantation. FASEB Journal. 1994;8(14):1122-1130.
Lu, Christopher Y. ; Khair-El-Din, Tarik A. ; Dawidson, Ingemar A. ; Butler, Thomas M. ; Brasky, Kathleen M. ; Vazquez, Miguel A. ; Sicher, Stanley C. / Xenotransplantation. In: FASEB Journal. 1994 ; Vol. 8, No. 14. pp. 1122-1130.
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