Scientists created 'synthetic' embryo with a brain without using egg or sperm cells

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Natural (left) and synthetic (right) embryos side by side to show comparable brain and heart formation.
Natural (left) and synthetic (right) embryos side by side to show comparable brain and heart formation.

Amadei/Handford/CU 

Genetic engineering experts at the University of Cambridge have produced a "synthetic" mouse embryo without using egg or sperm cells.

The embryos produced using stem cells were able to start developing a heart, brain, and other organs for up to a week, according to a press release published by the university on Thursday.

"It's an absolutely fantastically complex stage of development, and it has extremely relevant meaning for the rest of our life," said Magdalena Zernicka-Goetz, a Cambridge professor of mammalian development and stem cell biology, at a press conference announcing the findings.

"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," added Zernika also the lead author of the study.

The researchers believe their findings will one day help explain why many human pregnancies fail early in development and may even inform future efforts to create lab-grown organs for transplantation.

To a certain extent, researchers have learned how to develop already created embryos in the lab, as well as how to create artificial but simplistic models of embryos or individual organs—advances that have helped overcome some of these obstacles.

However, this new study claimed to be one of the first successful attempts at creating a functional mouse embryo from scratch.

The study of naturally developed embryos has provided scientists with numerous biological insights. But, many aspects of early development in living creatures are difficult to observe, the paper noted.

Embryos survived up to eight and a half days

The scientists created embryos by combining three different types of embryonic stem cells in the exact right combination and environment, allowing them to communicate with one another and mimicking what happens naturally during embryonic development.

The cells then began to form the fundamental structures of an embryo and progressed through the early stages of development, which included the formation of a yolk sac, brain, and beating heart. The embryos survived for up to eight and a half days.

Scientists created 'synthetic' embryo with a brain without using egg or sperm cells
Natural (left) and synthetic (right) embryos side by side to show comparable brain and heart formation.

Claim from Israel

The UK team is not the first to claim the creation of a synthetic mouse embryo.

On August 3rd, Interesting Engineering reported a similar claim of Israeli scientists creating a synthetic mouse embryo without using sperm or egg cells, but only stem cells taken "from the skin."

The UK authors argue that their work had been going through the review process for about a year, even before the Israel paper was submitted for publication, and that their model is more complex than any other model to date.

"This is really the first model that allows you to study brain development in the context of the whole developing mouse embryo," said Zernicka.

In 2021, the Israeli team demonstrated that it was possible to grow embryos in a beaker for up to six days. The Cambridge team said they are working on their own approach as well, reported Gizmodo.

Research can 'help' in early failed pregnancies

The researchers believe that this study will eventually help identify the numerous reasons why pregnancies can fail early on, even before people are aware of them.

Up to 50 percent of all pregnancies may end in miscarriage, according to the March of Dimes, an Arlington, Va.-based organization. However, estimates may vary.

"So many pregnancies fail around this time, before most women realize they are pregnant," said Zernicka.

"This period is the foundation for everything else that follows in pregnancy. If it goes wrong, the pregnancy will fail."

Many embryos created through in-vitro fertilization, on the other hand, can fail to implant or grow. If nothing else, simply studying these earliest stages of growth up close could provide scientists with all sorts of information on how we become the way we are, said the researchers.

If the UK research team's methods with human stem cells are successful in the future, they could be used to guide the development of synthetic organs for patients in need of a transplant.

The study, which was first published in Nature, is the result of years of research by scientists at the University of Cambridge.

Study abstract:

Embryonic stem cells (ESC) can undergo many aspects of mammalian embryogenesis in vitro1–5, but their developmental potential is substantially extended by interactions with extraembryonic stem cells, including trophoblast stem cells (TSCs), extraembryonic endoderm stem cells (XEN), and inducible-XEN cells (iXEN)6–11. Here, we assembled stem-cell derived embryos in vitro from mouse ESCs, TSCs and iXEN cells and showed that they recapitulate whole natural mouse embryo development in utero to day 8.5. Our embryo model displays head-folds with defined forebrain and midbrain regions and develops a beating heart-like structure, a trunk comprising a neural tube and somites, a tail bud containing neuromesodermal progenitors, a gut tube, and primordial germ cells. This complete embryo model develops within an extra-embryonic yolk sac that initiates blood island development. Importantly, we demonstrate that the neurulating embryo model assembled from Pax6 knockout-ESCs aggregated with wild-type TSCs and iXENs recapitulates the ventral domain expansion of the neural tube that occurs in natural, ubiquitous Pax6 knockout embryos. Thus, these complete embryoids are a powerful in vitro model for dissecting the roles of diverse lineages and genes in development. Our results demonstrate the self-organization ability of embryonic and two types of extra-embryonic stem cells to reconstitute mammalian development through and beyond gastrulation to neurulation and early organogenesis.

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