Cardiac xenotransplantation: Progress toward the clinic

Christopher G A McGregor, Sumeet S. Teotia, Guerard W. Byrne, Marian G. Michaels, Jack M. Risdahl, Johannes M. Schirmer, Henry D. Tazelaar, Randall C. Walker, John S. Logan

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Background. Animal organs could satisfy the demand for solid organ transplants, which currently exceeds the limited human donor supply. Hyperacute rejection, the initial immune barrier to successful xenotransplantation, has been overcome with pig donors transgenic for human complement regulatory proteins. Delayed xenograft rejection, thought to be mediated by anti-pig antibodies predominantly to Gal antigens, is currently regarded as the major barrier to successful xenotransplantation. A median graft survival of 90 days in the life-supporting position is considered a reasonable initial standard for consideration of entry to the clinic. Methods. A series of 10 heterotopic heart transplants from CD46 transgenic pigs to baboons was completed. Immunosuppression consisted of splenectomy, Rituximab (Anti-CD20), tacrolimus, sirolimus, corticosteroids, and TPC. Thymoglobulin (Rabbit Anti-Thymocyte Globulin) was used to treat putative rejection episodes. Results. Median graft survival was 76 days (range 56-113 days, n=9). Only three grafts were lost to rejection. The remaining grafts lost were due to recipient mortality with baboon cytomegalovirus (BCMV) being the major cause (n=4). No cellular infiltrates were present as a manifestation of rejection. Three hearts showed chronic graft vasculopathy. Conclusions. The median survival of 76 days in this group of heterotopic porcine-to-baboon cardiac xenografts represents a major advance over the median 27-day survival reported in the literature. Cellular rejection may not constitute a direct major barrier to xenotransplantation. A median survival of 90 days may be achievable with better control of BCMV infection. If further studies in the orthotopic position replicate these outcomes, criteria considered appropriate for clinical application of cardiac xenotransplantation would be approached.

Original languageEnglish (US)
Pages (from-to)1569-1575
Number of pages7
JournalTransplantation
Volume78
Issue number11
DOIs
StatePublished - Dec 15 2004

Fingerprint

Heterologous Transplantation
Papio
Transplants
Swine
Graft Survival
Heterografts
Survival
Animal Structures
Antilymphocyte Serum
Cytomegalovirus Infections
Tacrolimus
Splenectomy
Sirolimus
Cytomegalovirus
Immunosuppression
Anti-Idiotypic Antibodies
Adrenal Cortex Hormones
Complement System Proteins
Rabbits
Antigens

Keywords

  • Preclinical cardiac xenotransplantation

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

McGregor, C. G. A., Teotia, S. S., Byrne, G. W., Michaels, M. G., Risdahl, J. M., Schirmer, J. M., ... Logan, J. S. (2004). Cardiac xenotransplantation: Progress toward the clinic. Transplantation, 78(11), 1569-1575. https://doi.org/10.1097/01.TP.0000147302.64947.43

Cardiac xenotransplantation : Progress toward the clinic. / McGregor, Christopher G A; Teotia, Sumeet S.; Byrne, Guerard W.; Michaels, Marian G.; Risdahl, Jack M.; Schirmer, Johannes M.; Tazelaar, Henry D.; Walker, Randall C.; Logan, John S.

In: Transplantation, Vol. 78, No. 11, 15.12.2004, p. 1569-1575.

Research output: Contribution to journalArticle

McGregor, CGA, Teotia, SS, Byrne, GW, Michaels, MG, Risdahl, JM, Schirmer, JM, Tazelaar, HD, Walker, RC & Logan, JS 2004, 'Cardiac xenotransplantation: Progress toward the clinic', Transplantation, vol. 78, no. 11, pp. 1569-1575. https://doi.org/10.1097/01.TP.0000147302.64947.43
McGregor CGA, Teotia SS, Byrne GW, Michaels MG, Risdahl JM, Schirmer JM et al. Cardiac xenotransplantation: Progress toward the clinic. Transplantation. 2004 Dec 15;78(11):1569-1575. https://doi.org/10.1097/01.TP.0000147302.64947.43
McGregor, Christopher G A ; Teotia, Sumeet S. ; Byrne, Guerard W. ; Michaels, Marian G. ; Risdahl, Jack M. ; Schirmer, Johannes M. ; Tazelaar, Henry D. ; Walker, Randall C. ; Logan, John S. / Cardiac xenotransplantation : Progress toward the clinic. In: Transplantation. 2004 ; Vol. 78, No. 11. pp. 1569-1575.
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