Domesticated cynomolgus monkey embryonic stem cells allow the generation of neonatal interspecies chimeric pigs
Domesticated cynomolgus monkey embryonic stem cells allow the generation of neonatal interspecies chimeric pigs
复制标题
驯化食蟹猴胚胎干细胞可产生新生种间嵌合猪
DOI：
10.1007/s13238-019-00676-8
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发表时间：
2020-02-01
期刊：
影响因子：
21.1
通讯作者：
Zhou, Qi
中科院分区：
文献类型：
--
作者：
Fu, Rui;Yu, Dawei;Zhou, Qi
通过注射多能干细胞(PSC)来补充胚泡被认为是产生异种器官的最有前途的方法。然而，伦理问题阻碍了对处于胚胎发育后期的人类嵌合体的研究。灵长类胚胎干细胞具有与人类胚胎干细胞相似的多能性，是研究种间嵌合和器官发生的良好模型。然而，灵长类胚胎干细胞是否可以用于异种移植仍不清楚。在这项研究中，我们评估了食蟹猴ESCs(CmESCs)在猪体内的嵌合能力，因为它们与人类有许多相似之处，是很好的宿主。我们报道了一种优化的培养液，可以增强cmESCs的抗凋亡能力，促进嵌合胚胎的发育，将驯化的cmESCs(D-ESCs)注射到猪囊胚中，分化为所有三个胚层的细胞。此外，我们还获得了两个新生儿种间嵌合体，在其中我们观察到了组织特异性的D-ESC分化。综上所述，这些结果证明了D-ESCs在猪模型中整合和分化为功能细胞的能力，在不同的新生组织中嵌合率为0.001-0.0001。我们相信，这项工作将促进异种器官发生的未来发展，使我们更接近通过种间囊胚互补在大型动物模型中生产组织特异性功能细胞和器官。
Blastocyst complementation by pluripotent stem cell (PSC) injection is believed to be the most promising method to generate xenogeneic organs. However, ethical issues prevent the study of human chimeras in the late embryonic stage of development. Primate embryonic stem cells (ESCs), which have similar pluripotency to human ESCs, are a good model for studying interspecies chimerism and organ generation. However, whether primate ESCs can be used in xenogenous grafts remains unclear. In this study, we evaluated the chimeric ability of cynomolgus monkey (Macaca fascicularis) ESCs (cmESCs) in pigs, which are excellent hosts because of their many similarities to humans. We report an optimized culture medium that enhanced the anti-apoptotic ability of cmESCs and improved the development of chimeric embryos, in which domesticated cmESCs (D-ESCs) injected into pig blastocysts differentiated into cells of all three germ layers. In addition, we obtained two neonatal interspecies chimeras, in which we observed tissue-specific D-ESC differentiation. Taken together, the results demonstrate the capability of D-ESCs to integrate and differentiate into functional cells in a porcine model, with a chimeric ratio of 0.001-0.0001 in different neonate tissues. We believe this work will facilitate future developments in xenogeneic organogenesis, bringing us one step closer to producing tissue-specific functional cells and organs in a large animal model through interspecies blastocyst complementation.