Cardiac xenotransplantation: Recent preclinical progress with 3-month median survival

Christopher G A McGregor, William R. Davies, Keiji Oi, Sumeet S. Teotia, Johannes M. Schirmer, Jack M. Risdahl, Henry D. Tazelaar, Walter K. Kremers, Randall C. Walker, Guerard W. Byrne, John S. Logan

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Objectives: Transplantation is limited by a lack of human organ donors. Organs derived from animals, most likely the pig, represent a potential solution to this problem. For the heart, 90-day median graft survival of life-supporting pig hearts transplanted to nonhuman primates has been considered a reasonable standard for entry into the clinical arena. Overcoming the immune barrier to successful cardiac xenotransplantation is most appropriately first explored with the non-life-supporting heterotopic model. Methods: We performed a series of 7 heterotopic heart transplantations from CD46 transgenic pigs to baboons using a combination of therapeutic agents largely targeted at controlling the synthesis of anti-pig antibodies. Rituximab (anti-CD20) and Thymoglobulin (rabbit antithymocyte globulin [ATG]; SangStat Medical Corp, Fremont, Calif) were used as induction therapy. Baseline immunosuppression consisted of splenectomy, tacrolimus, sirolimus, steroids, and TPC (an anti-Gal antibody therapeutic). Rejection events were not treated. Results: By using Kaplan-Meier analysis, median graft survival was 96 days (range, 15-137 days; 95% confidence interval, 38-99 days). Only 2 grafts were lost as a result of rejection, as defined by cessation of graft palpation. There was no evidence of a consumptive coagulopathy, infectious complications were treatable, and no posttransplantation lymphoproliferative disorders occurred. No cellular infiltration was observed. Conclusions: This study reports the longest median survival to date (96 days) of pig hearts transplanted heterotopically into baboons. Duplication of these results in the orthotopic life-supporting position could bring cardiac xenotransplantation to the threshold of clinical application.

Original languageEnglish (US)
JournalJournal of Thoracic and Cardiovascular Surgery
Volume130
Issue number3
DOIs
StatePublished - Sep 2005

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Heterologous Transplantation
Swine
Survival
Papio
Graft Survival
Anti-Idiotypic Antibodies
Heterotopic Transplantation
Animal Structures
Transplants
Antilymphocyte Serum
Lymphoproliferative Disorders
Palpation
Kaplan-Meier Estimate
Tacrolimus
Splenectomy
Sirolimus
Heart Transplantation
Immunosuppression
Primates
Therapeutics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Cardiac xenotransplantation : Recent preclinical progress with 3-month median survival. / McGregor, Christopher G A; Davies, William R.; Oi, Keiji; Teotia, Sumeet S.; Schirmer, Johannes M.; Risdahl, Jack M.; Tazelaar, Henry D.; Kremers, Walter K.; Walker, Randall C.; Byrne, Guerard W.; Logan, John S.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 130, No. 3, 09.2005.

Research output: Contribution to journalArticle

McGregor, CGA, Davies, WR, Oi, K, Teotia, SS, Schirmer, JM, Risdahl, JM, Tazelaar, HD, Kremers, WK, Walker, RC, Byrne, GW & Logan, JS 2005, 'Cardiac xenotransplantation: Recent preclinical progress with 3-month median survival', Journal of Thoracic and Cardiovascular Surgery, vol. 130, no. 3. https://doi.org/10.1016/j.jtcvs.2005.04.017
McGregor, Christopher G A ; Davies, William R. ; Oi, Keiji ; Teotia, Sumeet S. ; Schirmer, Johannes M. ; Risdahl, Jack M. ; Tazelaar, Henry D. ; Kremers, Walter K. ; Walker, Randall C. ; Byrne, Guerard W. ; Logan, John S. / Cardiac xenotransplantation : Recent preclinical progress with 3-month median survival. In: Journal of Thoracic and Cardiovascular Surgery. 2005 ; Vol. 130, No. 3.
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