Ethical Blastocyst

The human embryo was collected from laboratory cells

Kirill Stasevich, Science and Life (nkj.ru )

Two research groups at once, at the University of Texas Southwestern Medical Center and at Monash University, reported in Nature that they managed to create a full-fledged human embryo at the blastocyst stage using laboratory methods. This is the name of one of the earliest stages of development – at the blastocyst stage, the embryo has not yet penetrated into the uterine wall, but is already ready to do it.

The human blastoid is a pseudo–embryo corresponding to the blastocyst stage. The nuclei of cells are colored blue. Photo: UT Southwestern

What is a blastocyst? After fertilization, the mammalian egg divides for the first few days until it turns out to be something like a bubble. There are three types of cells in this bubble. Those that surround it around the perimeter form the so-called trophoblast, or trophectoderm. The trophoblast cells will then form the placenta. Most of the volume inside the bubble is just a cavity, which is called the blastocyst cavity. But in one place, a cell mass forms on the inside of the bubble wall, which is again called the internal cell mass. It consists of an epiblast and a hypoblast. The hypoblast cells will then give the germ sac, which helps the embryo to feed and breathe at the earliest stages of development, and the chorion is another germ shell that will participate in the formation of the placenta. But the embryo body itself will begin to develop from epiblast cells.

With the development of molecular and cellular biology, researchers began to try to simulate a blastocyst in the laboratory. This makes sense not only from the point of view of fundamental knowledge about how the embryo develops, but also for practical reasons: many developmental pathologies and unsuccessful pregnancies begin with problems at the blastocyst stage. A few years ago, a laboratory blastocyst was assembled from mouse stem cells – the resulting cell structure was called a blastoid to distinguish it from a natural blastocyst. And now the same thing happened with human cells.

The main problem was to find stem cells similar to blastocyst cells. Researchers from the University of Texas took them from two sources. Firstly, these were real human blastocyst cells. Once a human blastocyst was taken for scientific research, disassembled into cells, and since then they have been preserved for experiments. (Germ cells are potentially immortal if properly maintained.)

Secondly, germ cells can be obtained from ordinary adult cells – these will be so-called induced pluripotent stem cells. Induced – because they are created by processing ordinary cells with special molecular signals. As a result, for example, skin cells lose specialization and fall into a deep embryonic childhood, when they could endlessly divide. Germ cells are able to turn into any other, so they are called pluripotent. We have written many times about such stem cells; their properties do not differ or almost do not differ from real germ cells.

The researchers grew the cells in a special vessel that allowed them to form a three-dimensional structure. That is, if stem cells wanted to create a blastocyst (blastoid), nothing would have prevented them. Of course, molecular factors were added to the nutrient medium, which were supposed to incline dividing cells to form a bubble with trophoblast, epiblast and hypoblast.

Another group of researchers, at Monash University, also worked with specialized cells of adults. But these cells were not converted into induced stem cells, but they ensured that blastocyst cells of three types immediately appeared among them. That is, the first research team "reset" the genetic activity of mature cells to the very, very initial embryonic state, and then launched a program of embryonic development in them - and the dividing cells themselves turned into trophoblast, epiblast and hypoblast cells. And the second team immediately tried to get trophoblast, epiblast and hypoblast cells, which were combined into a pseudo-embryo-blastoid. In the first case, the blastocyst was grown, in the second, it was assembled from a cellular constructor (more precisely, the parts of the constructor found themselves and joined into the desired structure).

In both cases, everything worked more or less successfully: human blastoids were formed on the 6-8 day of cell culture cultivation and with 20 percent success. They were the same size and structure as the real ones, and consisted of about the same number of cells. The gene activity in the artificial blastocyst was also the same as in the real one, ready to be implanted into the uterus. Actually, when the implantation conditions were simulated for the obtained blastoids, they were ready for it: they were attached to the cell culture, which depicted the uterine wall, and began to develop further. They developed embryonic organs to the point that some pseudoembryons prepared their cells to create a placenta.

That is, in principle, cellular structures obtained in this way may well serve as a model for studying the human embryo at the moment when it is preparing to take root in the uterus. Although the Nature portal writes about the inevitable ethical questions that always arise with the word "embryo", these questions will obviously not be as acute as if we were talking about a real embryo obtained by merging an egg and a sperm. However, before they begin to study something on human blastoids, it is necessary to adjust the methods by which they are obtained.

So far, pseudoembryons obtained as described above develop at different speeds, and even different types of cells within the same blastoid can also develop at slightly different speeds – although in real embryos everything is strictly synchronized. Finally, a group of cells remained in the blastoids, which does not belong to either the trophoblast, epiblast, or hypoblast, and researchers have yet to understand what these cells are and how to get rid of them.

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