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 journalArticlepeer-review

141 Scopus citations


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)
Pages (from-to)844.e1-844.e9
JournalJournal of Thoracic and Cardiovascular Surgery
Issue number3
StatePublished - Sep 2005
Externally publishedYes

Bibliographical note

Funding Information:
O. Eickelberg is supported by the Juvenile Diabetes Foundation International (#10-2000-71). Part of this study was supported by a grant from Fresenius Medical Care, Austria. We are grateful for the generous help and advice of M. Kashgarian during the performance of these studies.


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