Artificially created early stages of human embryos

Blastoids

Color-tagged blastoids grown from skin cells (Image: Monash University)

For the first time, researchers in the laboratory have created so-called blastoids – cell structures that resemble an early stage in embryonic development. Two research teams independently chose different approaches: while one group reprogrammed human skin cells, the other used embryonic stem cells. The result in both cases: structures whose structure and function are similar to that of human blastocysts, as they arise a few days after the egg cell is fertilized. In contrast to blastocysts, however, the artificially created blastoids cannot grow into embryos. Instead, they can be used as model systems for medical research.

At the beginning of a pregnancy there is a fusion of the sperm and the egg. The fertilized egg then begins to divide and after a few days forms the so-called blastocyst. This consists of various embryonic cells from which, after implantation in the uterine lining, the embryo itself, as well as the placenta and the amniotic cavity, develop. Research on this early phase of human development was previously only possible on blastocysts that were generated during artificial insemination and donated for research purposes. However, since the blastocysts could theoretically develop into a viable embryo, their investigation is ethically problematic and strictly regulated.

Blastocyst-like structures made from skin cells

Two research teams have now independently developed an alternative: A team led by Xiaodong Liu from Monash University in Australia reprogrammed human skin cells so that they were returned to a stem cell stage. In a special nutrient medium, they then differentiated into embryonic cells and formed a three-dimensional structure that comes very close to a blastocyst. According to Liu and colleagues, these so-called iBlastoids (short for “induced blastoids”) have all the typical components that blastocysts have: the cell types that would form the embryo in a blastocyst, those for the placenta, and those that make up the blastocoil, a cavity filled with fluid, develops.

“However, iBlastoids are not completely identical to a blastocyst,” explains Liu’s colleague Jose Polo. For example, they lack the egg shell that comes from the egg during normal fertilization and surrounds the early blastocyst. In addition, there were additional, unknown cell types in the blastoids that do not occur in blastocysts. And the different cell types from which the embryo and placenta could theoretically arise seemed to develop asynchronously. Human life could therefore not grow out of the blastocysts.

No development into an embryo possible

At the same time as Liu and colleagues, researchers led by Leqian Yu from the University of Texas published similar results. Instead of using skin cells, Yu’s group turned to embryonic stem cells from which they cultivated structures that they call “human blastoids”. “These structures are similar to human blastocysts in terms of structure, size, number of cells and composition,” the researchers report. “Genetically, the blastoids are also comparable to blastocysts.” But although the artificially created structures share many properties with blastocysts before they are implanted in the uterus, they could not create an embryo either.

That is precisely what makes them interesting for research. “Human blastoids provide an easily accessible, scalable, and versatile alternative to blastocysts for studying early human development, understanding early pregnancy loss, and gaining insight into early developmental defects,” write Yu and colleagues. Polo is also convinced: “iBlastoids will enable scientists to study the very early stages of human development and some of the causes of infertility, congenital diseases and the effects of toxins and viruses on early embryos – without the use of human blastocysts.” also drive the development of new therapies.

Ethical issues

According to current law, blastoids are not considered human embryos, so research on them is less strictly regulated. While blastocysts may be cultured for a maximum of 14 days, longer research would also be possible on blastoids. Nevertheless, both research teams stopped the growth of the blastoids after a few days in order to comply with the 14-day rule that applies to embryos. “Apparently the authors wanted public approval of their work before they crossed that line,” said Martin Johnson, Professor Emeritus of Reproductive Science at the University of Cambridge. “So there is work to be done for scientists to explain both the limits and the potential benefits of blastoid technology.”

With the previous blastoids, development into an embryo is impossible due to numerous limitations. However, the more they are optimized, the more similar they become to human blastocysts. “This will inevitably lead to bioethical questions,” write Yi Zheng and Jianping Fu of the University of Michigan in a comment on the studies that was published in the journal Nature with them. “For many people, studying human blastoids will be less ethical than studying natural human blastocysts. Others, however, could see research on human blastoids as a way of engineering human embryos. ”It is therefore important to have a public discussion about the scientific significance of this research, but also about the social and ethical issues involved.

Sources: Xiaodong Liu (Monash University, Clayton, Australia) et al., Nature, doi: 10.1038 / s41586-021-03372-y, Leqian Yu (University of Texas, Dallas, USA) et al., Nature, doi: 10.1038 / s41586-021-03356-y

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