To guide the development of their synthetic embryo, the researchers put together cultured stem cells representing each of the three types of tissue in the right proportions and environment to promote their growth and communication with each other, eventually self-assembling into an embryo. "This accessibility allows us to manipulate genes to understand their developmental roles in a model experimental system." "The stem cell embryo model is important because it gives us accessibility to the developing structure at a stage that is normally hidden from us due to the implantation of the tiny embryo into the mother's womb," said Zernicka-Goetz. Over the past decade, Professor Zernicka-Goetz's group in Cambridge has been studying these earliest stages of pregnancy, in order to understand why some pregnancies fail and some succeed.
If it goes wrong, the pregnancy will fail." "This period is the foundation for everything else that follows in pregnancy. "So many pregnancies fail around this time, before most women realise they are pregnant," said Zernicka-Goetz, who is also Professor of Biology and Biological Engineering at Caltech.
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Many pregnancies fail at the point when the three types of stem cells begin to send mechanical and chemical signals to each other, which tell the embryo how to develop properly. One of these extraembryonic stem cell types will become the placenta, which connects the fetus to the mother and provides oxygen and nutrients and the second is the yolk sac, where the embryo grows and where it gets its nutrients from in early development. In the first week after fertilisation, three types of stem cells develop: one will eventually become the tissues of the body, and the other two support the embryo's development. This has been the dream of our community for years, and major focus of our work for a decade and finally we've done it."įor a human embryo to develop successfully, there needs to be a 'dialogue' between the tissues that will become the embryo, and the tissues that will connect the embryo to the mother. "It's just unbelievable that we've got this far. "Our mouse embryo model not only develops a brain, but also a beating heart, all the components that go on to make up the body," said Zernicka-Goetz, Professor in Mammalian Development and Stem Cell Biology in Cambridge's Department of Physiology, Development and Neuroscience. Additionally, the results could be used to guide repair and development of synthetic human organs for transplantation. The team say their results, the result of more than a decade of research that progressively led to more and more complex embryo-like structures and reported in the journal Nature, could help researchers understand why some embryos fail while others go on to develop into a healthy pregnancy.
This is a further point in development than has been achieved in any other stem cell-derived model. Unlike other synthetic embryos, the Cambridge-developed models reached the point where the entire brain, including the anterior portion, began to develop. The stem cells self-organised into structures that progressed through the successive developmental stages until they had beating hearts and the foundations of the brain, as well as the yolk sac where the embryo develops and gets nutrients from in its first weeks. By inducing the expression of a particular set of genes and establishing a unique environment for their interactions, the researchers were able to get the stem cells to 'talk' to each other. The researchers mimicked natural processes in the lab by guiding the three types of stem cells found in early mammalian development to the point where they start interacting.
The team, led by Professor Magdalena Zernicka-Goetz, developed the embryo model without eggs or sperm, and instead used stem cells - the body's master cells, which can develop into almost any cell type in the body.
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