Pig-to-non-human primate heart transplantation: The final step toward clinical xenotransplantation?

Bruno Reichart, Matthias Längin, Julia Radan, Maren Mokelke, Ines Buttgereit, Jiawei Ying, Ann Kathrin Fresch, Tanja Mayr, Lara Issl, Stefan Buchholz, Sebastian Michel, Reinhard Ellgass, Maks Mihalj, Stefanie Egerer, Andrea Baehr, Barbara Kessler, Elisabeth Kemter, Mayuko Kurome, Valeri Zakhartchenko, Stig SteenTrygve Sjöberg, Audrius Paskevicius, Luise Krüger, Uwe Fiebig, Joachim Denner, Antonia W. Godehardt, Ralf R. Tönjes, Anastasia Milusev, Robert Rieben, Riccardo Sfriso, Christoph Walz, Thomas Kirchner, David Ayares, Karen Lampe, Uwe Schönmann, Christian Hagl, Eckhard Wolf, Nikolai Klymiuk, Jan Michael Abicht, Paolo Brenner

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The demand for donated human hearts far exceeds the number available. Xenotransplantation of genetically modified porcine organs provides an alternative. In 2000, an Advisory Board of the International Society for Heart and Lung Transplantation set the benchmark for commencing clinical cardiac xenotransplantation as consistent 60% survival of non-human primates after life-supporting porcine heart transplantations. Recently, we reported the stepwise optimization of pig-to-baboon orthotopic cardiac xenotransplantation finally resulting in consistent success, with 4 recipients surviving 90 (n = 2), 182, and 195 days. Here, we report on 4 additional recipients, supporting the efficacy of our procedure. Results: The first 2 additional recipients succumbed to porcine cytomegalovirus (PCMV) infections on Days 15 and 27, respectively. In 2 further experiments, PCMV infections were successfully avoided, and 3-months survival was achieved. Throughout all the long-term experiments, heart, liver, and renal functions remained within normal ranges. Post-mortem cardiac diameters were slightly increased when compared with that at the time of transplantation but with no detrimental effect. There were no signs of thrombotic microangiopathy. The current regimen enabled the prolonged survival and function of orthotopic cardiac xenografts in altogether 6 of 8 baboons, of which 4 were now added. These results exceed the threshold set by the Advisory Board of the International Society for Heart and Lung Transplantation. Conclusions: The results of our current and previous experimental cardiac xenotransplantations together fulfill for the first time the pre-clinical efficacy suggestions. PCMV-positive donor animals must be avoided.

Original languageEnglish
Pages (from-to)751-757
Number of pages7
JournalJournal of Heart and Lung Transplantation
Volume39
Issue number8
Early online date2020
DOIs
Publication statusPublished - 2020 Aug 1

Subject classification (UKÄ)

  • Surgery

Free keywords

  • costimulation blockade
  • graft growth
  • heart preservation
  • orthotopic heart transplantation
  • xenotransplantation

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