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Consistent success in life-supporting porcine cardiac xenotransplantation

Author

Listed:
  • Matthias Längin

    (University Hospital, LMU Munich
    Walter Brendel Centre of Experimental Medicine, LMU Munich)

  • Tanja Mayr

    (University Hospital, LMU Munich
    Walter Brendel Centre of Experimental Medicine, LMU Munich)

  • Bruno Reichart

    (Walter Brendel Centre of Experimental Medicine, LMU Munich)

  • Sebastian Michel

    (University Hospital, LMU Munich)

  • Stefan Buchholz

    (University Hospital, LMU Munich)

  • Sonja Guethoff

    (Walter Brendel Centre of Experimental Medicine, LMU Munich
    University Hospital, LMU Munich)

  • Alexey Dashkevich

    (University Hospital, LMU Munich)

  • Andrea Baehr

    (Gene Center, LMU Munich)

  • Stefanie Egerer

    (Gene Center, LMU Munich)

  • Andreas Bauer

    (University Hospital, LMU Munich)

  • Maks Mihalj

    (University Hospital, LMU Munich)

  • Alessandro Panelli

    (Walter Brendel Centre of Experimental Medicine, LMU Munich)

  • Lara Issl

    (Walter Brendel Centre of Experimental Medicine, LMU Munich)

  • Jiawei Ying

    (Walter Brendel Centre of Experimental Medicine, LMU Munich)

  • Ann Kathrin Fresch

    (Walter Brendel Centre of Experimental Medicine, LMU Munich)

  • Ines Buttgereit

    (Walter Brendel Centre of Experimental Medicine, LMU Munich)

  • Maren Mokelke

    (Walter Brendel Centre of Experimental Medicine, LMU Munich)

  • Julia Radan

    (Walter Brendel Centre of Experimental Medicine, LMU Munich)

  • Fabian Werner

    (University Hospital, LMU Munich)

  • Isabelle Lutzmann

    (Walter Brendel Centre of Experimental Medicine, LMU Munich)

  • Stig Steen

    (Lund University and Skåne University Hospital)

  • Trygve Sjöberg

    (Lund University and Skåne University Hospital)

  • Audrius Paskevicius

    (Lund University and Skåne University Hospital)

  • Liao Qiuming

    (Lund University and Skåne University Hospital)

  • Riccardo Sfriso

    (University of Bern)

  • Robert Rieben

    (University of Bern)

  • Maik Dahlhoff

    (Gene Center, LMU Munich)

  • Barbara Kessler

    (Gene Center, LMU Munich)

  • Elisabeth Kemter

    (Gene Center, LMU Munich)

  • Mayuko Kurome

    (Gene Center, LMU Munich)

  • Valeri Zakhartchenko

    (Gene Center, LMU Munich)

  • Katharina Klett

    (Technical University of Munich
    LMU Munich
    DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance)

  • Rabea Hinkel

    (Technical University of Munich
    LMU Munich
    DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance)

  • Christian Kupatt

    (Technical University of Munich
    DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance)

  • Almuth Falkenau

    (Institute of Veterinary Pathology, LMU Munich)

  • Simone Reu

    (Medical Faculty, LMU Munich)

  • Reinhard Ellgass

    (University Hospital, LMU Munich)

  • Rudolf Herzog

    (University Hospital, LMU Munich)

  • Uli Binder

    (XL-protein GmbH)

  • Günter Wich

    (Wacker-Chemie AG)

  • Arne Skerra

    (Technical University of Munich)

  • David Ayares

    (Revivicor)

  • Alexander Kind

    (Technical University of Munich)

  • Uwe Schönmann

    (German Primate Centre)

  • Franz-Josef Kaup

    (German Primate Centre)

  • Christian Hagl

    (University Hospital, LMU Munich)

  • Eckhard Wolf

    (Gene Center, LMU Munich)

  • Nikolai Klymiuk

    (Gene Center, LMU Munich)

  • Paolo Brenner

    (Walter Brendel Centre of Experimental Medicine, LMU Munich
    University Hospital, LMU Munich)

  • Jan-Michael Abicht

    (University Hospital, LMU Munich
    Walter Brendel Centre of Experimental Medicine, LMU Munich)

Abstract

Heart transplantation is the only cure for patients with terminal cardiac failure, but the supply of allogeneic donor organs falls far short of the clinical need1–3. Xenotransplantation of genetically modified pig hearts has been discussed as a potential alternative4. Genetically multi-modified pig hearts that lack galactose-α1,3-galactose epitopes (α1,3-galactosyltransferase knockout) and express a human membrane cofactor protein (CD46) and human thrombomodulin have survived for up to 945 days after heterotopic abdominal transplantation in baboons5. This model demonstrated long-term acceptance of discordant xenografts with safe immunosuppression but did not predict their life-supporting function. Despite 25 years of extensive research, the maximum survival of a baboon after heart replacement with a porcine xenograft was only 57 days and this was achieved, to our knowledge, only once6. Here we show that α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and thrombomodulin require non-ischaemic preservation with continuous perfusion and control of post-transplantation growth to ensure long-term orthotopic function of the xenograft in baboons, the most stringent preclinical xenotransplantation model. Consistent life-supporting function of xenografted hearts for up to 195 days is a milestone on the way to clinical cardiac xenotransplantation7.

Suggested Citation

  • Matthias Längin & Tanja Mayr & Bruno Reichart & Sebastian Michel & Stefan Buchholz & Sonja Guethoff & Alexey Dashkevich & Andrea Baehr & Stefanie Egerer & Andreas Bauer & Maks Mihalj & Alessandro Pane, 2018. "Consistent success in life-supporting porcine cardiac xenotransplantation," Nature, Nature, vol. 564(7736), pages 430-433, December.
  • Handle: RePEc:nat:nature:v:564:y:2018:i:7736:d:10.1038_s41586-018-0765-z
    DOI: 10.1038/s41586-018-0765-z
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