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    Pig-to-non-human primate heart transplantation:
    the final step toward clinical xenotransplantation? (2020)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Reichart, Bruno
    Längin, Matthias
    Radan, Julia
    Mokelke, Maren
    Buttgereit, Ines
    Ying, Jiawei
    Fresch, Ann Kathrin
    Mayr, Tanja
    Issl, Lara
    Buchholz, Stefan
    Michel, Sebastian
    Ellgass, Reinhard
    Mihalj, Maks
    Egerer, Stefanie
    Baehr, Andrea
    Kessler, Barbara
    Kemter, Elisabeth
    Kurome, Mayuko
    Zakhartchenko, Valeri
    Steen, Stig
    Sjöberg, Trygve
    Paskevicius, Audrius
    Krüger, Luise
    Fiebig, Uwe
    Denner, Joachim (WE 5)
    Godehardt, Antonia W.
    Tönjes, Ralf R.
    Milusev, Anastasia
    Rieben, Robert
    Sfriso, Riccardo
    Walz, Christoph
    Kirchner, Thomas
    Ayares, David
    Lampe, Karen
    Schönmann, Uwe
    Hagl, Christian
    Wolf, Eckhard
    Klymiuk, Nikolai
    Abicht, Jan-Michael
    Brenner, Paolo
    Quelle
    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
    Bandzählung: 39
    Heftzählung: 8
    Seiten: 751 – 757
    ISSN: 1053-2498
    Sprache
    Englisch
    Verweise
    URL (Volltext): https://www.sciencedirect.com/science/article/abs/pii/S1053249820315564
    DOI: 10.1016/j.healun.2020.05.004
    Pubmed: 32527674
    Kontakt
    Institut für Virologie

    Robert-von-Ostertag-Str. 7-13
    14163 Berlin
    +49 30 838 51833
    virologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    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.