Consistent success in life-supporting porcine cardiac xenotransplantation.

Längin, Matthias; Mayr, Tanja; Reichart, Bruno; Michel, Sebastian; Buchholz, Stefan; Guethoff, Sonja; Dashkevich, Alexey; Baehr, Andrea; Egerer, Stefanie; Bauer, Andreas; Mihalj, Maks; Panelli, Alessandro; Issl, Lara; Ying, Jiawei; Fresch, Ann Kathrin; Buttgereit, Ines; Mokelke, Maren; Radan, Julia; Werner, Fabian; Lutzmann, Isabelle; ... (2018). Consistent success in life-supporting porcine cardiac xenotransplantation. Nature, 564(7736), pp. 430-433. Macmillan Journals Ltd. 10.1038/s41586-018-0765-z

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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 need. Xenotransplantation of genetically modified pig hearts has been discussed as a potential alternative. 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 baboons. 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 once. 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 xenotransplantation.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiovascular Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Herz und Gefässe
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50
09 Interdisciplinary Units > Microscopy Imaging Center (MIC)

UniBE Contributor:

Mihalj, Maks; Sfriso, Riccardo and Rieben, Robert

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0028-0836

Publisher:

Macmillan Journals Ltd.

Language:

English

Submitter:

Daniela Huber

Date Deposited:

06 Mar 2019 16:11

Last Modified:

06 Dec 2019 15:30

Publisher DOI:

10.1038/s41586-018-0765-z

Related URLs:

PubMed ID:

30518863

BORIS DOI:

10.7892/boris.124854

URI:

https://boris.unibe.ch/id/eprint/124854

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