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2.
Nature ; 564(7736): 430-433, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30518863

RESUMEN

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.


Asunto(s)
Trasplante de Corazón , Xenoinjertos/trasplante , Papio , Porcinos , Trasplante Heterólogo , Animales , Anticuerpos/análisis , Anticuerpos/sangre , Proteínas del Sistema Complemento/análisis , Enzimas/sangre , Fibrina/análisis , Galactosiltransferasas/deficiencia , Galactosiltransferasas/genética , Xenoinjertos/patología , Humanos , Hígado/enzimología , Masculino , Proteína Cofactora de Membrana/genética , Proteína Cofactora de Membrana/metabolismo , Miocardio/enzimología , Necrosis , Perfusión , Recuento de Plaquetas , Tiempo de Protrombina , Trombomodulina/genética , Trombomodulina/metabolismo , Factores de Tiempo
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