They create a new generation of synthetic embryos without ovules, sperm or uterus, and with a more developed brain

The world was surprised a few weeks ago when the Israeli laboratory led by the biologist Jacob Hanna published a study in the journal ‘Cell’ showing that he had been able to cultivate synthetic embryos beyond the eighth day of development from mouse embryonic cells, but without using sperm, eggs, or even a mouse uterus. Now, a team from the University of Cambridge has emulated this same experiment, achieving a somewhat higher success rate than Hanna’s group and a brain with more complex structures. The results have just been published in the journal ‘Nature’.

From mouse embryonic cellscell groups were created that were introduced in a kind of ‘mechanical uterus‘ – actually devised by Hanna, who is also an author of the Cambridge study – where embryos float in small boats with a solution full of nutrients. The beakers are enclosed in a rotating cylinder that keeps them in constant motion, simulating how blood and nutrients flow to the placenta. The device also replicates the atmospheric pressure of a mouse’s uterus.

This is how the researchers, headed by the biologist Magdalena Zernicka-Goetz, professor in the department of mammalian development and stem cell biology in the Department of Physiology and Neuroscience at Cambridge, managed to mimic the natural processes of reproduction but in the laboratory; To do this, they ‘guided’ the stem cells to organize themselves into structures that progressed through successive stages of development until the embryos presented beating hearts and the foundations of a future brain – although the system does not fully mimic all the stages of development-, in addition to structures outside the embryo, such as the yolk sac and the placenta.

However, other structures, such as the umbilical cord, which makes it impossible to implant these embryos in a uterus so that they can be born. “In their current form, these structures look like and show the gene expression patterns of embryos, but they are not real embryos. The gold standard for a mouse embryo would be to implant it into the uterus of a receptive female and develop it to term. But they lack the structures that would allow them to implant in the uterus and develop further,” says Zernicka-Goetz.

Differences and similarities with the Israeli team

The base of both experiments is the same and the development time too: 8.5 days (more or less, half the gestation time of a mouse pregnancy, which is about 19 or 20 days); however, there are small changes that have produced different consequences. Unlike Hanna’s experiment, the Zernicka-Goetz team’s embryos used a mixture of other types of embryonic cells that led to further development of some structures, such as the brain anterior, the most voluminous and complex area of ​​this organ. “But our mouse embryo model not only develops a brain, but also a beating heart and all the components that make up the body,” says Zernicka-Goetz. “It’s amazing that we’ve come this far. This has been the dream of our group for years and the main focus of our work for a decade. We finally made it.”

Furthermore, in this experiment, the success rate was 1%, which while still low, exceeds that of the Israeli team’s tests, which reached 0.5%, according to their calculations. “The frequency of these synthetic embryos is very low: many collapse a few days before maturing and all have many defects in the organization of tissues and organs,” he explains to ABC Alfonso Martinez Arias, ICREA research professor and researcher in Bioengineering Systems-MELIS at Pompeu Fabra University. “At the moment, it is not clear how this system will replace the natural method, which provides embryos more efficiently and robustly.” Even so, Martínez Arias points out that the most positive point of both articles “is that it gives an idea that it is a real result and not a carom.” “It’s an important advance, but too troublesome to think that it’s going to change the trajectory of research quickly,” he says.

For its part, Louis Montoliu, a researcher at the National Center for Biotechnology of the CSIC (CNB-CSIC), adds in this regard in statements to SMS Spain: «Without a doubt we are facing a new technological revolution, still very inefficient, but with enormous potential. It recalls such spectacular scientific advances as the birth of Dolly the sheep, which we met in 1997, reconstructing an embryo with the nucleus of a somatic cell, or inducible pluripotent embryonic cells, iPS, described by Yamanaka in 2006, which led him to obtain the Nobel Prize in Physiology or Medicine in 2012, shared with John Gurdon, pioneer of animal cloning in amphibians. A revolution that naturally also raises new ethical dilemmas, if we ever think of transferring these experiments to the human species for the generation of synthetic human embryos, perhaps in order to use them to obtain new tissues or organs to repair or replace those that are damaged, as Hanna has already proposed to explore, through a company created by him ad hoc».

future applications

Both experiments point to the close possibility of studying the early embryonic stages of mammals without using animal embryos. “This period of human life is very mysterious, so to be able to see it happen in a lab dish, to have access to these individual stem cells, to understand why so many pregnancies fail and how we might prevent that from happening is quite special.” Zernicka-Goetz points out.

The two laboratories also indicate that there are possibilities, in the long term, of being able to use this system to create synthetic organs ‘à la carte’ for transplants. “It should also be possible to affect and cure adult organs using the knowledge we have about how they are made,” says the biologist. “The embryo is the best 3D bioprinter. The best method to create suitable organs and tissues », says Hanna, who has stated that she has started testing with her own cells to create synthetic human embryos.

What’s more, the website of the company he founded to study this field, Renewal Bio, explains that his goal is “to make humanity younger and healthier by harnessing the power of stem cell technology,” which it can be “applied to a wide variety of human ailments, including infertility, genetic disease, and longevity.” Promises aside, without a doubt the field of synthetic embryos is positioned as one of the scientific fields with the greatest potential and, also, the greatest debate.

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