Scientists have created an embryo from skin cells and learned how to grow embryos without a uterus

Two teams of scientists immediately announced that they had created a model of a human embryo without an egg and a sperm cell, writes Forbes.

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An imitation blastocyst - an early stage of embryo development - was grown from fibroblasts, reprogrammed connective tissue cells. This will circumvent the ban on such experiments in most countries. Let's figure out how “real” the embryo is and what the future holds for these discoveries.

Conception without fertilization

Typically, embryos are grown in the laboratory from donor fertilized eggs. In the case of cloning, sperm can be discarded. Since the mid-tenths, it has become clear that it is possible to grow embryos in a test tube without the participation of germ cells at all. The blastocyst consists of three types of cells, from which the tissues of the fetus, the placenta and the yolk sac are then formed. And they get it all from stem cells.

For the first time, scientists from the University of Cambridge (UK) managed to create a "fetus without parents" in 2017. They took embryonic and extraembryonic trophoblastic stem cells (from which the placenta is formed) from the mouse and placed them on a three-dimensional extracellular matrix. There they self-organized into a structure that resembled an ordinary mouse embryo in structure.

However, on the fourth day of the experiment, its development stopped - there was no access to nutrients, as in the mother's body.

Stem cell pregnancy

The following year, the experiment was repeated by researchers from the University of Utrecht in the Netherlands. Like their British colleagues, they created a mouse embryo from two types of stem cells - embryonic and trophoblastic. However, the Dutch have moved on. The blastocyst grown by them has formed all types of cells necessary for further development.

Moreover, when implanted into the uterus of an animal, the blastocyst caused pregnancy. True, the authors of the work emphasized that they did not get a completely real embryo and therefore the female could not bear it and give birth.

In 2019, scientists from the Salk Institute for Biological Research (USA) also initiated pregnancy in mice by transplanting embryos obtained from just one somatic cell. It was taken from the body of an adult animal, reprogrammed and propagated - thus the culture of embryonic stem cells appeared.

Then they were reprogrammed again, turning them into the so-called improved pluropotent cells, and treated with a cocktail of special signaling substances - those that, during natural embryonic development, cause the differentiation of the trophoblast (from which the placenta is formed) and the internal cell mass (from which the embryo tissues are formed).

As a result, in 15% of cases, blastoids grew from them - structures similar to blastocysts in cellular composition and gene expression.

When the resulting blastoids were transferred to the uterus of mice, about seven percent were able to attach there. As the researchers noted, in the body of females they developed for about a week, but significantly lagged behind ordinary embryos, and then died out.

Imitation of a human

Hypothetically, a similar trick should have worked with human cells. An embryo obtained in this way would circumvent the current rather harsh rules that directly prohibit the creation of human embryos for research purposes. And without this, it is impossible to figure out what actually happens in the early stages of development.

And on March 12, a group of scientists from the California Institute of Technology (USA) and the University of Cambridge announced that they had grown human embryos using only stem and somatic cells of adults. In fact, the researchers have perfected the methodology by which in 2017 they created the world's first mouse "fetus without parents." However, their results have only appeared on the bioRxiv preprint site and have not yet been reviewed.

Two other works - by biologists from the United States and Australia - were published simultaneously on March 18 in Nature. Both of them managed to grow from the cells of the connective tissue of an adult a structure that is similar in properties, shape and size to a human blastocyst. As in the experiments with mice, it was called a blastoid.

The Americans first reprogrammed fibroblast cells into pluripotent stem cells. And then they were placed in a special three-dimensional culture dish, where they were exposed to signal substances. As a result, the embryo was formed. Like a real human blastocyst, it contained three types of cells, from which the placenta, yolk sac, and tissues of the embryo itself would subsequently form.

On the subject: 28-year-old American gave birth to a child, conceived 27 years ago

The Australians took a different path. They reprogrammed adult cells in such a way that several important genes were expressed in them in the same way as in the three types of cells contained in the blastocyst. Then they were placed in a three-dimensional dish, where they were treated with a cocktail of signaling substances. After six to eight days, they received a human embryo model.

In both experiments, only about 20% of the reprogrammed cells turned into blastoids, which is comparable to the results of experiments with mice.

In addition, scientists simulated the transfer of the resulting embryos into the uterus - for obvious reasons, such a procedure cannot be carried out in reality. Pseudo-implantation was successful, but already on the tenth or eleventh day, the embryos stopped developing.

As Vyacheslav Chernykh, head of the laboratory of genetics of reproductive disorders at the Bochkov Medical Genetics Research Center, Vyacheslav Chernykh, explained in a conversation with RIA Novosti, the research is about a not quite “real” human embryo.

“Although the artificially created blastocyst contains the necessary elements (the outer layer of cells, the cavity - the blastocoel - and the part that resembles the inner cell mass), there are some embryological deficiencies. In particular, violations of the dynamics and synchronicity of development, morphological differences in the structure of the structures of the embryo, genetic and epigenetic inconsistencies, etc. ", - he noted.

Not quite human

It is likely that society as a whole will be more tolerant of research on such models than experiments on real embryos, researchers from the University of Michigan (USA) say in the Nature editorial. So far, the main ethical question that needs to be addressed is whether the 14-day rule applies to them.

Today, human embryos obtained experimentally are destroyed 14 days after fertilization. In some countries, violation of this norm is punishable by law, in others, experiments with such embryos reject ethical committees and deprive them of funding.

“Since such a“ cellular creation ”is obtained artificially, it is not entirely forbidden to grow it. However, it is definitely impossible to transfer it to the woman's uterus and this should be prohibited! Perhaps it makes sense to do them for fundamental research of the mechanisms of human development in the early stages after fertilization of the egg. Moreover, if there is no ban that such embryoids can be cultured for more than 14 days, ”explained Vyacheslav Chernykh.

If the ban on blastoids is lifted, then scientists will probably be able to understand not only the causes of miscarriages and failures in IVF, but also to find out the mechanisms of a number of hereditary pathologies, including cardiovascular diseases and some types of diabetes.

Scientists have grown an embryo outside the uterus

Professor Jacob Hanna of the Weizmann Institute of Science and his team were able to grow a mouse embryo outside the uterus. They have developed a method that allows you to track the development of the embryo, as well as understand how genes work and identify birth defects and malformations. Habr.

Hannah explains that information about the embryonic development of mammals is obtained either from observations of this process in frogs and fish, or from static images of dissected mouse embryos.

According to the scientist, the idea of ​​growing embryos outside the uterus has been around since before the 1930s, but earlier experiments had limited success. Hannah's team decided to renew this effort.

Over the course of seven years, the researchers developed a two-step process and were able to grow normally developing mouse embryos outside the uterus within six days. This is about a third of their gestation period, which is 20 days. By this time, the body and organs are already forming in the embryos.

In the first phase, which lasted about two days, the researchers worked with embryos several days old - just after they were to be implanted into the uterus. At this stage, the embryos were balls of 250 identical stem cells. They were placed on a special nutrient medium, and the balls were fixed inside the laboratory glassware. After that, the embryos double and triple in size, three layers are formed: inner, middle and outer.

After two days, when the embryos entered the next stage of development - the formation of organs from each of the layers - they needed additional conditions. Scientists placed them in a nutrient solution in tiny beakers, placing them on rollers that allowed the solution to mix continuously. Thus, embryos could grow without maternal blood flow to the placenta.

The team compared the obtained samples with embryos removed from pregnant mice at the appropriate time period. They turned out to be almost identical.

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In subsequent experiments, the scientists placed genes in the embryos that marked the growing organs with fluorescent colors. The success of this attempt showed that further experiments involving various genetic and other manipulations should yield reliable results.

According to Hannah, scientists can now insert genes into embryonic cells, infect them with viruses and conduct other experiments. The team is confident that this method will reduce the cost and speed up the developmental biology research process, as well as reduce the need for laboratory animals.

The next step in the lab is to check if the embryo removal step in pregnant mice can be skipped. Scientists intend to create artificial embryos from stem cells.

Among other things, they hope to find out why many pregnancies fail to implant an embryo, why the implantation window is so small, as well as how stem cells gradually lose their properties and under what conditions of pregnancy the fetus will develop abnormally.

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