1. Consistent success in life-supporting porcine cardiac xenotransplantation
- Author
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Längin, Matthias, Mayr, Tanja, Reichart, Bruno, Michel, Sebastian, Buchholz, Stefan, Guethoff, Sonja, and Dashkevich, Alexey
- Subjects
Heart transplantation -- Analysis -- Research ,Xenotransplantation -- Research ,Genetic engineering -- Usage ,Cardiac patients ,Animal genetic engineering ,Immunotherapy ,Galactose ,Genetically modified organisms ,Antigenic determinants ,Surgery ,Genetically modified animals ,Heart failure ,Swine ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - 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.sup.1-3. Xenotransplantation of genetically modified pig hearts has been discussed as a potential alternative.sup.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.sup.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.sup.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.sup.7. [alpha]1,3-galactosyltransferase-knockout pig hearts that express human CD46 and human thrombomodulin require non-ischaemic preservation with continuous perfusion and post-transplantation growth control to ensure long-term orthotopic function of the xenograft in baboons., Author(s): Matthias Längin [sup.1] [sup.2] , Tanja Mayr [sup.1] [sup.2] , Bruno Reichart [sup.2] , Sebastian Michel [sup.3] , Stefan Buchholz [sup.3] , Sonja Guethoff [sup.2] [sup.3] , Alexey Dashkevich [...]
- Published
- 2018
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