They create a new generation of synthetic embryos without eggs, 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 Hannah published a study in the journal 'Cell' proving 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 uterus of mouse. Now, a team from the University of Cambridge has emulated this same experiment, achieving a slightly 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 cells, cell groups were created that were introduced in a kind of 'mechanical uterus' - devised in fact by Hanna, who is also the 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 and simulates 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, led 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, they managed to imitate 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 completely mimic all the structures. development phases -, in addition to structures on the outside of the embryo, such as the yolk sac and placenta.

However, other structures were not present, such as the umbilical cord, which does not make it possible 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.

The basis of both experiments is the same and the development time is also: 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 greater development of some structures, such as the brain previous, 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 incredible that we have come this far. This has been the dream of our group for years and the main focus of our work for a decade. "We have finally achieved it."

Furthermore, in this experiment, the success rate was 1%, which, although 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 Martínez 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 in a more efficient and robust way." Even so, Martínez Arias points out that the most positive point of both articles "is that it gives the idea that it is a real result and not a carom." "It is an important advance, but with too many problems to think that it will change the trajectory of research quickly," he says.

For its part, Lluis Montoliu, 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 is reminiscent of scientific advances as spectacular as the birth of Dolly the sheep, which we met in 1997, reconstructing an embryo with the nucleus of a somatic cell, or the inducible pluripotent embryonic cells, the iPS, described by Yamanaka in 2006, which led him to obtaining 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 with the aim of using 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.

Both experiments point to the near possibility of studying the early embryonic stages of mammals without the need to use animal embryos. "This period of human life is very mysterious, so being able to see it happen in a lab dish, having access to these individual stem cells, understanding why so many pregnancies fail and how we could prevent that from happening is pretty special," says Zernicka-Goetz.

The two laboratories also indicate that there are possibilities, in the long term, of being able to use this system to create 'à la carte' synthetic organs for transplants. "It should also be possible to affect and cure adult organs using the knowledge we have about how they are manufactured," 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 begun testing with her own cells to create synthetic human embryos.

What's more, on the website of the company he founded to study this field, Renewal Bio, it is explained that its goal is to “make humanity younger and healthier, harnessing the power of stem cell technology,” which can be “applied to a wide variety of human ailments, including infertility, genetic diseases 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.