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Nature. 2018 Dec;564(7736):430-433. doi: 10.1038/s41586-018-0765-z. Epub 2018 Dec 5.

Consistent success in life-supporting porcine cardiac xenotransplantation.

Author information

1
Department of Anaesthesiology, University Hospital, LMU Munich, Munich, Germany.
2
Transregional Collaborative Research Center 127, Walter Brendel Centre of Experimental Medicine, LMU Munich, Munich, Germany.
3
Transregional Collaborative Research Center 127, Walter Brendel Centre of Experimental Medicine, LMU Munich, Munich, Germany. bruno.reichart@med.uni-muenchen.de.
4
Department of Cardiac Surgery, University Hospital, LMU Munich, Munich, Germany.
5
Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich, Germany.
6
Department of Cardiothoracic Surgery, Lund University and Skåne University Hospital, Lund, Sweden.
7
Department for BioMedical Research (DMBR), University of Bern, Bern, Switzerland.
8
I. Medizinische Klinik, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
9
Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany.
10
DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
11
Institute of Veterinary Pathology, LMU Munich, Munich, Germany.
12
Institute of Pathology, Medical Faculty, LMU Munich, Munich, Germany.
13
XL-protein GmbH, Freising, Germany.
14
Wacker-Chemie AG, Munich, Germany.
15
Munich Center for Integrated Protein Science (CIPS-M) and Lehrstuhl für Biologische Chemie, School of Life Sciences Weihenstephan, Technical University of Munich, Munich, Germany.
16
Revivicor, Blacksburg, VA, USA.
17
Chair of Livestock Biotechnology, School of Life Sciences Weihenstephan, Technical University of Munich, Munich, Germany.
18
German Primate Centre, Göttingen, Germany.

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.

PMID:
30518863
DOI:
10.1038/s41586-018-0765-z

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