The study of embryonic development as a consequence of complex organisms arising from a single cell is one of the most fascinating fields of biology. As late as the 18th century, there was fierce debate over whether the process started from a miniature infant delivered to the woman’s womb by male semen, which is the conventional idea of preformation, or from a fertilized egg that divides and differentiates into specialized cells and organs, which is the theory of epigenesis. Since the epigeneticists won the debate, much has been learned about the specific mechanisms behind the development of an embryo, and now cutting edge research in this field has ventured into synthetic biology. In just three centuries, scientists have performed the astounding feat of developing the first synthetic self-developing embryo using stem cells in mice.
Today’s embryonic research involves an intricate network of stem cells interacting outside of the organism to result in development. Mammalian embryonic research is readily on the rise, as scientists aim to reconcile the complexity of mammalian development with the difficulty of working with miniscule eggs. “The human zygote is only 100 µm in diameter,” approximately the same as that of a human hair, which inevitably leads to challenges when it comes to zygote manipulation (2).
A basic recap of embryonic development in mammals begins with the implanting of the embryo within the uterus which leads to interactions amongst embryonic and extraembryonic tissues. Subsequently, the embryonic epiblast cells polarize and lead to development of the ectodermal cavity and the mesoderm. The mesoderm is responsible for the synthesis of muscle, cartilage, connective tissue, bone and more, and the ectoderm, for forming the skin, eyes, and brain.
The aim of the experiment was to induce, in mice, the morphing of the stem cells “into primitive embryos that perfectly replicated the internal structures that emerge during normal development in the womb” (1). This was done by first isolating the artificial cells in culture for one week, which is a third of a mouse’s gestation period. Two types of stem cells were utilized at the origin of the study, an embryonic stem cell and trophoblast stem cells, which are “precursors of the differentiated cells of the placenta. At the end of this week, the stem cells had developed into either placental or embryonic cells, due to their respective origins. Thereafter began the process of specialization into the germ layers, and then more developed organs. Researchers hope that the study will contribute to our understanding of key principles of pregnancy, and represents progress toward the synthesis of human embryos outside of the womb.
In yet another study conducted on mice, “Epiblast cells were implanted into cultures, as embryonic stem cells, because they can be maintained indefinitely” (3). The researchers attempted to use both embryonic and extraembryonic, trophoblastic stem cells to induce mouse embryogenesis in vitro, instead of allowing for naturally occurring in vivo embryogenesis. Once the embryonic and trophoblast stem cells were mixed in culture for a period of 5 days, the cells began to differentiate into 2 distinct types, the mesoderm and ectoderm. Results presented a marked similarity in post implantation embryo of mice either in vivo or in vitro, a feat that scientists cheered as even the anatomy of the self-developed mice was accurate (3). However, one significant difference was the absence of a primitive endoderm in the in vitro mice, despite the presence of trophoblast cells, leading to the absence of a yolk sac. A yolk sac would provide important nourishment as well as a complex network of blood vessels, and so its absence halted further development into a healthy fetus.
“Professor Robin Lovell-Badge, a stem cell biologist at The Francis Crick Institute in London, said one challenge was that scientists have not yet worked out how to extract trophoblast cells from human embryos” (1). In mice, two types of stem cells were used to create synthetic embryos. In order to transfer this research to artificially create the first synthetic self-developing human embryo, however, scientists must first develop methods to isolate trophoblast stem cells. Nevertheless, science has indeed triumphed in successfully completing this experiment in mice, and has paved the way to future research in monitoring development before implantation, shedding light not only on the reason behind the high miscarriage rate but also the mechanics behind birth defects.
- Devlin, Hannah. “Cambridge Scientists Create First Self-Developing Embryo from Stem Cells.” The Guardian, Guardian News and Media, 2 Mar. 2017
- Gilbert SF. Early Mammalian Development.Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. NCBI
- Sarah Ellys Harrison, Berna Sozen, Neophytos Christodoulou, Christos Kyprianou, Magdalena Zernicka-Goetz. “Assembly of embryonic and extraembryonic stem cells to mimic embryogenesis in vitro”. Science. 2 Mar. 2017