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.α1,3-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.

中文翻译：

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维持生命的猪心脏异种移植取得持续成功

心脏移植是晚期心力衰竭患者的唯一治疗方法，但同种异体供体器官的供应远远不能满足临床需要1-3。转基因猪心脏的异种移植已被讨论为一种潜在的替代方法4。缺乏半乳糖-α1,3-半乳糖表位（α1,3-半乳糖基转移酶敲除）并表达人膜辅助因子蛋白（CD46）和人血栓调节蛋白的基因多修饰猪心脏在狒狒异位腹部移植后存活了长达 945 天5 . 该模型证明长期接受具有安全免疫抑制的不一致异种移植物，但不能预测其维持生命的功能。尽管经过 25 年的广泛研究，用猪异种移植物心脏置换后，狒狒的最大存活时间仅为 57 天，而据我们所知，这仅实现了一次 6。在这里，我们表明表达人 CD46 和血栓调节蛋白的 α1,3-半乳糖基转移酶敲除猪心脏需要非缺血性保存，持续灌注和控制移植后生长，以确保狒狒异种移植物的长期原位功能，这是最严格的临床前异种移植模型。异种移植心脏长达 195 天的持续生命支持功能是临床心脏异种移植的里程碑7.α1，