Li Biyi, Kwon Chulan
Division of Cardiology, Department of Medicine, Department of Biomedical Engineering, Department of Cell Biology, Institute for Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Biochem Biophys Rep. 2025 Jun 27;43:102120. doi: 10.1016/j.bbrep.2025.102120. eCollection 2025 Sep.
Blastocyst complementation offers an opportunity for generating transplantable whole organs from donor sources. Pluripotent stem cells (PSCs) have traditionally served as the primary donor cells due to their ability to differentiate into any type of body cell. However, the use of PSCs raises ethical concerns, particularly regarding their uncontrollable differentiation potential to undesired cell lineages such as brain and germline cells. To address this issue, various strategies have been explored, including the use of genetically modified PSCs with restricted lineage potential or lineage-specified progenitor cells as donors. In this study, we tested whether nascent mesendodermal cells (MECs), which appear during early gastrulation, can be used as donor cells. To do this, we induced Bry-GFP MECs from mouse embryonic stem cells (ESCs) and introduced them into the blastocyst. While donor ESCs gave rise to various regions of embryos, including the heart, Bry-GFP MECs failed to contribute to the host embryos. This finding suggests that MECs, despite being specified from PSCs within a few days, lack the capacity to assimilate into the developing embryo.
囊胚互补为从供体来源生成可移植的完整器官提供了一个机会。多能干细胞（PSCs）传统上一直作为主要的供体细胞，因为它们能够分化成任何类型的体细胞。然而，PSCs的使用引发了伦理问题，特别是关于它们向不期望的细胞谱系（如脑细胞和生殖系细胞）的不可控分化潜力。为了解决这个问题，人们探索了各种策略，包括使用具有受限谱系潜力的基因改造PSCs或谱系指定的祖细胞作为供体。在这项研究中，我们测试了在原肠胚形成早期出现的新生中胚层细胞（MECs）是否可以用作供体细胞。为此，我们从小鼠胚胎干细胞（ESCs）中诱导出Bry-GFP MECs，并将它们引入囊胚。虽然供体ESCs产生了胚胎的各个区域，包括心脏，但Bry-GFP MECs未能对宿主胚胎做出贡献。这一发现表明，MECs尽管在几天内就从PSCs分化而来，但缺乏融入发育中胚胎的能力。
