Consistent success in life-supporting porcine cardiac xenotransplantation

Research output: Contribution to journalLetter

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.

Details

Authors
  • Matthias Längin
  • Tanja Mayr
  • Bruno Reichart
  • Sebastian Michel
  • Stefan Buchholz
  • Sonja Guethoff
  • Alexey Dashkevich
  • Andrea Baehr
  • Stefanie Egerer
  • Andreas Bauer
  • Maks Mihalj
  • Alessandro Panelli
  • Lara Issl
  • Jiawei Ying
  • Ann Kathrin Fresch
  • Ines Buttgereit
  • Maren Mokelke
  • Julia Radan
  • Fabian Werner
  • Isabelle Lutzmann
  • Audrius Paskevicius
  • Liao Qiuming
  • Riccardo Sfriso
  • Robert Rieben
  • Maik Dahlhoff
  • Barbara Kessler
  • Elisabeth Kemter
  • Katharina Klett
  • Rabea Hinkel
  • Christian Kupatt
  • Almuth Falkenau
  • Simone Reu
  • Reinhard Ellgass
  • Rudolf Herzog
  • Uli Binder
  • Günter Wich
  • Arne Skerra
  • David Ayares
  • Alexander Kind
  • Uwe Schönmann
  • Franz Josef Kaup
  • Christian Hagl
  • Eckhard Wolf
  • Nikolai Klymiuk
  • Paolo Brenner
  • Jan Michael Abicht
Organisations
External organisations
  • Skåne University Hospital
  • University of Bern
  • Klinikum rechts der Isar
  • German Centre for Cardiovascular Research
  • XL-protein GmbH
  • Wacker-Chemie AG
  • Revivicor, Inc
  • Technical University of Munich
  • Ludwig-Maximilian University of Munich
  • University Hospital Munich
  • German Primate Center
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cardiac and Cardiovascular Systems
  • Surgery
Original languageEnglish
Pages (from-to)430-433
Number of pages4
JournalNature
Volume564
Issue number7736
Publication statusPublished - 2018
Publication categoryResearch
Peer-reviewedYes