A man-made embryo has been created in a lab in a world first, raising hopes for the prevention of miscarriages.
An embryo normally requires the fertilisation of an egg with a sperm, and this then grows in the womb before birth.
Now, scientists from the Weizmann Institute of Science in Israel have shown that a synthetic version can be created using nothing but the stem cells of mice, with no conception.
They formed a beating heart, a brain and an intestinal tract in the same way as a natural embryo, researchers found.
The experiment opens the door for new forms of research into foetal development and miscarriages as well as a potential way to reduce animal experiments. In the future, the technique could also grow embryos as a stock of organs for harvest and transplantation.
In 2021, the team created a way to produce “naive” stem cells which have the ability to turn into any tissue in the body, ranging from neurons to skin cells. They also built a machine which 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 have been fertilised and the team wanted to create synthetic alternatives, bypassing all-natural steps.
The versatile naive mice stem cells were put into the machine, combining both the previous discoveries, with chemicals to aid the development of the placenta and the yolk sac, which are essential for embryo development.
Prof Jacob Hanna of Weizmann’s Molecular Genetics Department, who headed the research team, called the chemicals “a transient push” to help support the development.
The overwhelming majority of the experiments failed, but for 0.5 per cent of trials, one in 200, a progenital embryonic sphere was formed.
This minority of experiments then elongated and lasted for more than eight days, growing in the exact same way, and at the same rate, as a natural embryo.
A mouse pregnancy only lasts 20 days, so the 8.5-day-old embryos had by this point developed miniature, functioning organs, including a beating heart, a brain and an intestinal tract.
The researchers had labelled the cells with coloured tags so they could be viewed under a microscope, and they saw the synthetic embryo, made from no sex cells, was 95 per cent similar to a real mouse foetus.
Prof Hanna said the team now wants to unpick exactly how the cells know what to do, and how the instructions are relayed in order to produce organs in the right spot 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 modelling 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 fertilised eggs, the supply is vast and there are fewer logistical and ethical hurdles in the way of research.
The embryos are not real, Prof Hanna said, and if left to grow to full term would not produce live animals.
Israel, where the work was conducted, has ethical approval for these experiments to be done with human stem cells. The UK has similar laws, and this may open the door for such research, where synthetic human embryos are developed in a lab for study, experimentation and, ultimately, transplantation.
Researchers say the finding is a significant step forward for the 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 the reliability of the process must be improved as a priority before it can be employed widely.
“This will take time but it will be done,” he added.
“Importantly, it opens the door to similar studies with human cells, though there are many regulatory hoops to get through first.”
Dr James Briscoe, Assistant Research Director at the Francis Crick Institute in London, said synthetic human embryos are still a distant dream, but said the work is “a valuable proof of concept demonstration”.