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).
| Dokumententyp: | Zeitschriftenartikel |
|---|---|
| Fakultät: | Medizin |
| Fakultätsübergreifende Einrichtungen: | Center for Integrated Protein Science Munich (CIPSM) |
| Themengebiete: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
500 Naturwissenschaften und Mathematik > 540 Chemie |
| ISSN: | 0028-0836 |
| Sprache: | Englisch |
| Dokumenten ID: | 63116 |
| Datum der Veröffentlichung auf Open Access LMU: | 19. Jul. 2019, 12:12 |
| Letzte Änderungen: | 10. Sep. 2021, 14:13 |
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