Four keys to the new breakthrough in the race for synthetic human embryos

Four keys to the new breakthrough in the race for synthetic human embryos

A recent research Published in the prestigious magazine Nature He returned to the center of the scene an advance that, even today, amazes his own and others. Especially when analyzed under the gaze of two experts who, in the United Kingdom and Israel, fight to revolutionize the Medicine and its applications. In addition to providing solutions for diseases and conditions that afflict humanity.

According to the work recently done by the professor Jacob Hanna, of the Weizmann Institute of Science, the group of researchers he leads achieved Create complete models of human embryos from stem cells grown in the laboratory. In other words, they are embryos. Synthetic Cultivated outside the uterus until day 14.

As detailed in the study, These organisms had all the characteristic structures and compartments. of this stage, including placenta, yolk sac, chorionic sac and other external tissues that ensure the Dynamic and appropriate growth of the models. They also indicated that these tissues, which reach half a millimeter wide, were created by combining stem cells that were organized into structures that mimic the Three-dimensional organization of all known characteristics found in human embryos one to two weeks of age.

Although it may be similar news to the one announced a few months ago from England, the truth is that Israeli experts went a step further: “This is the First embryo model which has an organization of structural compartments and a morphological similarity to a human embryo on the 14th.” That is, they have almost all the defining characteristics of a post-implantation embryo (that is, at a stage after the moment when, in the case of a human being, it should be implanted in the uterus for growth).

To achieve this goal, the researchers used the method recently developed by Hanna to Reprogram pluripotent stem cells in order to turn the clock back even further: They reverted these cells to a previous state, known as naïve, and divided the cells into three groups. Those destined to become embryos were left as is, the others were treated only with chemicals, without the need for genetic modification, to activate certain genes. Shortly after mixing under optimized and specifically developed conditions, they formed groups, about 1% of which self-organized into complete embryo-like structures.

The Embryo-like structures based on stem cells (referred to as SEM) developed normally outside the uterus for 8 days, reaching a developmental stage equivalent to day 14 in human embryonic development. That is the point at which natural embryos acquire the internal structures that allow them to move on to the next stage: developing the progenitors of the body’s organs.

Faced with this reality, which seems to be overcome day by day, several aspects arise to analyze. From the ethical point of view to the race with his English peers, what is the situation of this technique in the world and what are the edges that are under the magnifying glass of science. What the experts had pointed out to Infobae when it was known, last June, the chance that a synthetic embryo reached 14 days of life.

In the world, according to the latest scientific publications, there are two groups of experts who develop this technique. It is a group of scientists led by Hanna in the Weizmann Institute of Science, Israel, and the one who heads the Professor Magdalena Żernicka-Goetz, of the University of Cambridge and the California Institute of Technology in the United Kingdom.

Before this new advance, from British soil had been announced the creation of “synthetic” human embryos from stem cells and without the need for eggs or sperm, which took place in mid-June. At the time, experts noted that these “models” resemble the early stages of development.They cautioned that it could provide crucial information about how genetic disorders or other factors impact this stage of life.

The information had been released at the annual meeting of the International Society for Stem Cell Research in Boston and days later a similar breakthrough was announced from Israel. As the British expert had highlighted, these “synthetic embryos”, do not have a beating heart and no “brain beginning”, but they have the rest of the cells. That is to say that are included those that make up “the placenta, yolk sac and the embryo itself“.

“Our human model is the first three-lineage human embryo model that specifies amnion and germ cells, egg and sperm precursor cells,” he said. Żernicka-Goetz to the British press. He added: “It’s beautiful and created entirely from embryonic stem cells,” he said.

For his part, Professor Hanna had stated to The Times of Israel, After the publication of a work in preprint version (without peer review) in a scientific journal, which “does not have a beating heart, nor a brain, but it has a very complex organization and is already beginning to show an early differentiation of tissues. All the elements of architecture are there and are in the right relationship and orientation with each other.”

Likewise, the Israeli expert explained that the “stem cell-derived embryo (SEM), which does not undergo genetic manipulation, is equivalent to a 14-day-old embryo.” “We had to create induced pluripotent stem cells and push them to develop,” Hanna said. He added: “Some of the media we use had been discussed before, but the three critical media are used recently by our group and are described in our paper.”

“Usually, we cannot mimic the very complex processes that occur during embryo development. To do this, we need to know which genes and proteins are turned on or off. Once we uncover them, we can add or reduce them. We do not know the human embryo and what it does to all its organs between day seven and day 28 of pregnancy. These three weeks are fast and critical, but it’s a black box.”

With this panorama, the idea of going a step further became latent and, a few hours ago, this advance gave rise to a more developed embryo and with other characteristic aspects of the development of an embryo present. That is why, in the face of this innovation, it is expected that the team led by Żernicka-Goetz will generate a new stage in this biological “race”.

Experts are conclusive when it comes to analyzing this advance: it is a revolutionary technique that manages to make synthetic human embryos from stem cells, leaving the egg and sperm in “oblivion”.

“The creation of synthetic stem cell embryos is an important advance in scientific research, as they have the ability to differentiate into different types of specialized cells. In the case of synthetic embryos, human pluripotent stem cells are used and cultured in a suitable environment to differentiate into embryonic cells and begin embryonic development, are created in vitro, developed outside a uterus, with characteristics similar to normal embryos“”, had indicated to Infobae The doctor Soledad Kleppe, medical specialist in Genetics and Metabolic Diseases at the High Complexity Medical Institute of the Italian Hospital.

Adrian Turjanski, expert and professor at the University of Buenos Aires, specialist in bioinformatics and scientific director of the company Bitgenia, dedicated to precision medicine, had highlighted in dialogue with Infobae that, thanks to this breakthrough, “They managed to create from stem cells, embryos, but They’re not necessarily going to end up equal to a human being.”

For his part, the doctor Paul Wappner, head of the Laboratory of Genetics and Molecular Physiology of the Leloir Institute and principal investigator of CONICET, meanwhile, had highlighted in dialogue with Infobae, that “in this case what they are doing is grabbing a cell of the body that is called undifferentiated, which has no identity, or anything. And, from that cell, it isDevelop an embryo. That is, they have found the methodology to achieve it.” While warning that the absence of a heart and a brain is related to the period of evolution of the embryo: “It is a misunderstanding, because it is not that they do not want it to have these organs, but that until now they have not reached that point of evolution.”

In that regard, Hernan Dopazo, PhD in Biological Sciences, Independent Researcher of the CONICET and Scientific Director of Biocodices, had highlighted in conversation with Infobae that “have come to generate a set of differentiated tissues (not organs) in the same synthetic structure that is very interesting. In the imaginary, when we say embryo we believe that it will give a complete individual, but this is not what has happened with the same structures of other species. This entity may resemble as much as possible a true embryonic structure, with the capacity for analysis beyond day 14, but the characterization of each of these tissues has to be greatly improved. The best comparison is with miscarriages donated to research.”

“The development of stem cells is revolutionizing science because we are beginning to understand, discover and give it uses that were not intended in the beginning. This possibility of being able to have cells that can differentiate from any other type of cell, can form tissues and organize themselves at the reproductive level, opened a lot of doors,” he had pointed out to Infobae Andres Gambini, Argentine scientist expert in cloning and embryo production in the laboratory, who currently works at The University of Queensland, Australia.

“The in vitro culture of up to seven days of life, any laboratory has it. We work with this kind of embryos, but to go beyond you need a more specialized type of cell culture, which they have developed, and it reached the 14th day of life,” he had told Infobae Claudio Bisioli, biologist (UBA), scientific director of Pregna Medicina Reproductiva, an in vitro fertilization clinic in Buenos Aires.

Beyond that it is about “A model” Similar to a human embryo, this technique opens up a range of possibilities in a scientific field that has applications both in fertility as in genetic diseases and Gestation, are the most named applications. But they are not the only ones.

“There are two applications, one is that of mere knowledge or Pure science. It is seeking knowledge for the sake of knowing. The other is what is called the applied science And this is difficult to study in utero. So, if one could study these structures in vitro, in our field specifically, we could have very valuable information about gestation and the possibility of getting pregnant. With this, we would have an abundance of very important information,” Bisioli explained.

In that tone, Turjanski warned that in this field, in “human beings you can study once they are already large. But these, not being reached by the Law because they are somehow synthetic, allows researchers to continue studying them beyond the limits imposed by the Law of 14 days. When you’re trying to understand what development is like or how a human being is formed, you have two options: in humans you study it, you look at it, you do diagnostic imaging, you open it, or you do anatomies. Instead, in embryos you can wait and see what happens.”

“The applications, for me, are of fundamental researchfundamentally. Not yet applied, because there is talk of creating organs, but for that it is not necessary to generate embryos. For me the key to this type of development is understand human development and its possible genetic failures or non-genetic. And when I think about future applications I mean the next 5 years. Beyond that, it is impossible for me to think about where it will continue without talking about spawns, clones and organ transplants,” Dopazo reflected. At the same time he affirmed that, in addition, “it could have immense applications in reproductive medicine, By helping patients with infertility problems, synthetic gems derived from the parents’ genome could be developed. But that’s another challenge.”

For its part, Kleppe added: Research with synthetic stem cell embryos is important for science, as it allowsDiscuss the different stages of embryonic development and see which genes are expressed at each moment. This is essential to understand what happens when things go wrong and to look for the causes of malformations or pregnancy losses. By not having a viable embryo, in theory, you can make an artificial model that allows you to see the different moments of development and then look for alterations in those genes that may be the causes of something malfunctioning.”

In the same way, Gambini considered it: “Obviously, this advance has super interesting consequences for treatments in fertility problems, in improving implementation rates and potential to open new doors of what would be, for example, the Organ production in the laboratory. But it is important to clarify that we are not talking about embryos themselves, but about cells that have mixed them and that resemble an embryo. It is very important to note that all attempts to make embryos from cells, without the participation of gametes, in mice, transferred to the uteruses of females, fail to develop live animals. On the other hand, these structures similar to a day 14 embryo, which they have managed to make, are structures that could not even be thought of transferring and ending in a birth, because the implantation period has already passed, which occurs inside the mother’s womb for it to be successful. “

An essential point of this advance relates to ethical dilemmas. As the British expert, who was backed by her Israeli counterpart, had pointed out, “It would be illegal to implant them in a patient’s uterus, and it’s not yet clear if these structures have the potential to continue maturing. beyond the early stages of development.”

“Obviously this advance brings a lot of ethical problems, because at one point it starts to be a human being, if it really looks very much like those synthetic embryos to the real ones. So far, what they saw is that they did not develop a brain, but it develops much of what looks like a human being. It’s quite disturbing how to make a laboratory human without the need for egg and sperm. And since they are not reached by the Law, those Embryos that are somehow synthetic, allows them to researchers to be able to continue studying them beyond the limits imposed by the Law. What do you mean? That you can, to study it, modify a part of its DNA and see how it evolves. In animals it can be done, especially in mice and it is about using that little animal as a disease model, “he said. Turjanski.

In turn Gambini had explained: “This brings an ethical dilemma because there is Absence of regulation. By definition they are not embryos, but are combined cells. The important thing is to recognize that they are not embryos as such, but that they are very similar structures embryos that one manages to produce by mixing stem cells, with different culture media and with different signaling. The strongest finding is that they have managed to produce absolutely all types of embryonic and extra-embryonic tissues, and this had not been achieved before. However, it is not a 100% natural embryo, but artificial.”

We should not think of them as human beings. because they cannot develop. Not for now and I do not think that in the short term we will see direct applications, before I would expect them from systems such as CRISPR and stem cells derived from human adults, “said the Independent researcher of CONICET, Dopazo. He added: “I think we are living through a stage of biology that is glorious. Never before have we experienced the possibilities we have today to change the destiny of families suffering from illnesses. It is a wonderful thing that we will have to learn to Use without fear, but with a lot of responsibility and ethical awareness.”

Bisioli added: “This is going to lead to a lot of things appearing. The opinion of all the experts, scientists, and people who work on this, is that embryos until they form the neural tube and do not begin to develop what is a nervous system, are not human but human cells. That is, they are not people, they are potentially people. Although it may border on some religious aspects, the vision of science, in general, is different.”


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