The scarcity of donor organs may be addressed in the future by using pigs to grow humanized organs with lower potential for immunological rejection after transplantation in humans. Previous studies have demonstrated that interspecies complementation of rodent blastocysts lacking a developmental regulatory gene can generate xenogeneic pancreas and kidney^1,2. However, such organs contain host endothelium, a source of immune rejection. We used gene editing and somatic cell nuclear transfer to engineer porcine embryos deficient in ETV2, a master regulator of hematoendothelial lineages^3,4,5,6,7. ETV2-null pig embryos lacked hematoendothelial lineages and were embryonic lethal. Blastocyst complementation with wild-type porcine blastomeres generated viable chimeric embryos whose hematoendothelial cells were entirely donor-derived. ETV2-null blastocysts were injected with human induced pluripotent stem cells (hiPSCs) or hiPSCs overexpressing the antiapoptotic factor BCL2, transferred to synchronized gilts and analyzed between embryonic day 17 and embryonic day 18. In these embryos, all endothelial cells were of human origin.

供体器官的稀缺性可能会在未来通过使用猪来培养人源化器官来解决，这些器官移植到人体后免疫排斥的可能性较低。以前的研究表明，缺乏发育调节基因的啮齿动物胚泡的种间互补可以产生异种胰腺和肾脏^1,2。然而，这些器官含有宿主内皮，这是一种免疫排斥反应的来源。我们使用基因编辑和体细胞核移植来设计缺乏ETV2的猪胚胎，ETV2是血内皮谱系的主要调节因子^3,4,5,6,7。ETV2-空猪胚胎缺乏造血内皮细胞谱系并且是胚胎致死的。与野生型猪卵裂球互补的胚泡产生了可行的嵌合胚胎，其造血内皮细胞完全来自供体。用人诱导多能干细胞 (hiPSC) 或过表达抗凋亡因子 BCL2 的 hiPSC 注射ETV2无效囊胚，转移到同步后备母猪中，并在胚胎第 17 天和胚胎第 18 天之间进行分析。在这些胚胎中，所有内皮细胞都是人类来源的。