A man-made embryo has been created in a laboratory in a world first, raising hopes for the prevention of miscarriages.
An embryo normally requires the fertilization of an egg with a sperm, and this then grows in the uterus before birth.
Now researchers from the Weizmann Institute of Science in Israel have shown that a synthetic version can be made using nothing but stem cells from mice, without conception.
They formed a beating heart, a brain and an intestinal tract in the same way as a natural embryo, researchers found.
The trial opens up new forms of research into fetal development and spontaneous abortions as well as a potential way to reduce animal testing. In the future, the technique could also grow embryos as a stock of organs for harvesting and transplantation.
In 2021, the team created a way to produce “naive” stem cells that have the ability to turn into any tissue in the body, from neurons to skin cells. They also built a machine that acts as an artificial womb and allows embryos to grow in their normal way.
But previous studies had all worked with real mouse eggs that had been fertilized, and the team wanted to create synthetic alternatives, bypassing all-natural steps.
The versatile naïve mouse stem cells were inserted into the machine, combining both the previous discoveries, with chemicals to help the development of the placenta and yolk sac, which are crucial for embryo development.
Prof Jacob Hanna of the Weizmann Department of Molecular Genetics, who led the research team, called the chemicals “a temporary push” to support development.
The overwhelming majority of experiments failed, but for 0.5 percent of the attempts, one in 200, a progenital embryonic sphere was formed.
This minority of experiments were then extended to more than eight days, growing in exactly the same way, and at the same rate, as a natural embryo.
A mouse pregnancy lasts only 20 days, so by this time the 8.5-day-old embryos had developed functioning miniature organs, including a beating heart, a brain and an intestinal tract.
The researchers had labeled the cells with colored markers so they could be seen under a microscope, and they saw that the synthetic embryo, made from no germ cells, was 95 percent similar to a real mouse embryo.
Prof Hanna said the team now wants to pick out exactly how the cells know what to do and how the instructions are relayed to produce organs in the right place at the right time.
He added that because the team’s mechanical womb and petri dish approach is transparent, they can track every step of an embryo’s development in extreme detail.
This, he says, “may prove useful for modeling birth and implantation defects of human embryos” to shed light on the hidden dynamics of embryo development, which may help explain the cause of some miscarriages.
And because the system only needs stem cells, not real fertilized eggs, the supply is large and there are fewer logistical and ethical obstacles in the way of research.
The embryos are not real, Prof Hanna said, and if allowed to grow to full term, will not produce live animals.
Israel, where the work was carried out, has ethical approval for these experiments to be done with human stem cells. The UK has similar laws and this could open the door to such research, where synthetic human embryos are developed in a laboratory for study, experimentation and, ultimately, transplantation.
Researchers say the discovery is a significant step forward for research, but add that there is still a long way to go in improving the technique.
Prof Alfonso Martinez Arias from the Universitat Pompeu Fabra (UPF) in Barcelona, called the findings a “potentially a significant development”, but said that the reliability of the process must be improved as a priority before it can be widely used.
“This will take time, but it will be done,” he added.
“Importantly, it opens the door to similar studies with human cells, although there are many regulatory hoops to jump through first.”
Dr James Briscoe, assistant director of research at the Francis Crick Institute in London, said synthetic human embryos were still a distant dream, but said the work was “a valuable proof of concept demonstration”.