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Laengin, Matthias; Mayr, Tanja; Reichart, Bruno; Michel, Sebastian; Buchholz, Stefan; Guethoff, Sonja; Dashkevich, Alexey; Bähr, 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; Steen, Stig; Sjoberg, Trygve; Paskevicius, Audrius; Qiuming, Liao; Sfriso, Riccardo; Rieben, Robert; Dahlhoff, Maik; Kessler, Barbara; Kemter, Elisabeth; Klett, Katharina; Hinkel, Rabea; Kupatt, Christian; Falkenau, Almuth; Reu, Simone; Ellgass, Reinhard; Herzog, Rudolf; Binder, Uli; Wich, Guenter; Skerra, Arne; Ayares, David; Kind, Alexander; Schönmann, Uwe; Kaup, Franz-Josef; Hagl, Christian; Wolf, Eckhard; Klymiuk, Nikolai; Brenner, Paolo and Abicht, Jan-Michael (2018): Consistent success in life-supporting porcine cardiac xenotransplantation. In: Nature, Vol. 564, No. 7736: pp. 430-433

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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 need(1-3). Xenotransplantation of genetically modified pig hearts has been discussed as a potential alternative(4). Genetically multi-modified pig hearts that lack galactose-alpha 1,3- galactose epitopes (alpha 1,3-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(5). 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(6). Here we show that alpha 1,3-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(7).

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