Consistent success in life-supporting porcine cardiac xenotransplantation

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, Stig Steen, Trygve Sjöberg, Audrius Paskevicius, Liao Qiuming, Riccardo Sfriso, Robert Rieben, Maik Dahlhoff, Barbara Kessler, Elisabeth Kemter, Mayuko Kurome, Valeri Zakhartchenko, 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 and Jan-Michael Abicht
Additional contact information
Matthias Längin: University Hospital, LMU Munich
Tanja Mayr: University Hospital, 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
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
Rabea Hinkel: Technical University of Munich
Christian Kupatt: Technical University of Munich
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
Jan-Michael Abicht: University Hospital, LMU Munich

Nature, 2018, vol. 564, issue 7736, 430-433

Abstract: 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.

Keywords: Human Thrombomodulin; Human Membrane Cofactor Protein; Terminal Cardiac Failure; Xenografted; Left Ventricular (LV) (search for similar items in EconPapers)
Date: 2018
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DOI: 10.1038/s41586-018-0765-z

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