Scientists grow a complete model of a human embryo, without using sperm or egg

Scientists at the Weizmann Institute have developed an entity that closely resembles an early human embryo, with no sperm, eggs or uterus.

The early stages of the embryo are crucial to its development, but difficult to study for ethical and technical reasons. Scientists have now succeeded in creating complete models of human embryos from stem cells grown in the lab and growing them outside the uterus until day 14 of life.

Behind this research is the Palestinian scientist Jacob Hanna, of the Weizmann Institute of Sciences (Israel), who already made this research public last June in an article published in a scientific repository (bioRxiv), without the review of other researchers. Their results will appear in the Wednesday scientific journal Nature.

The announcement of the creation of synthetic human embryos from stem cells was presented at a scientific conference in Boston last June.

The Israeli team says their ’embryo model’, made from stem cells, resembles a textbook example of a real 14-day embryo. It even released hormones that were positive on a pregnancy test in the laboratory.

The first few weeks after a sperm fertilizes an egg are a period of dramatic changes: from a collection of fuzzy cells to something that finally becomes recognizable on a baby scan. This crucial time is a major source of miscarriages and birth defects, but this is not yet well understood. “It’s a black box and not a cliché: our knowledge is very limited,” explains Professor Jacob Hanna of the Weizmann Institute of Science.

How the research was conducted

The team drew on their previous experience creating synthetic stem cell-based models of mouse embryos.

The synthetic embryos had all the characteristic structures and compartments of the first few weeks, including the placenta, yolk sac, chorionic sac, and other external tissues that ensured proper and dynamic growth of the models.

Structurally, they resemble natural embryos, even if they are not identical, the authors summarize in their article.

“Given their enormous complexity, the obtained human embryo models may provide an unprecedented opportunity to shed new light on the mysterious beginnings of the embryo,” said a statement from Weizmann.

In these early stages, the clump of cells implanted in the uterus on the seventh day becomes a well-structured embryo with organs within three to four weeks. “The drama takes place in the first month (…). This is still a big black box,” says Hanna.

Many pregnancy failures occur in the early weeks, as do birth defects.

He then used Hanna’s recently developed method of reprogramming pluripotent stem cells to turn back the clock even further: returning these cells to an even earlier state, known as “naive,” in which they can specialize into any type of cell.

This state corresponds to day 7 of the natural human embryo, around the time it implants in the womb.

The scientists divided the cells into three groups; those destined to become embryos remained as they are.

Those from the other groups were treated only with chemicals, without the need for genetic modification, to activate certain genes so that they would differentiate into one of the three types of tissue needed for the embryo: placenta, yolk sac or membrane. of the extraembryonic mesoderm that ultimately creates the chorionic sac.

Shortly after mixing under specially cultured and optimized conditions, the cells formed clumps, about 1% of which organized themselves into complete embryo-like structures.

“An embryo is self-driving by definition, we don’t have to tell it what to do, we just have to release its internally encoded potential,” says Hanna, for whom “it’s essential to select the right cell types at the right time.” to blend. beginning, which can only be derived from naive stem cells (…). Once this is done, the embryonic model itself says: go ahead!

The study has already led to a finding that, according to Weizmann, may open a new avenue for research into early pregnancy failure.

If the embryo is not sufficiently enveloped by placenta-forming cells on day 3 of the protocol (corresponding to day 10 in natural embryonic development), the internal structures, such as the yolk sac, cannot develop properly.

Teams behind artificial embryos

In addition to Hanna, there are other teams working in this field in a “scientific competition” involving controversy, including who beat whom and whether or not the results were disclosed according to scientific protocol (publication in a journal).

The other groups are Magdalena Zernicka-Goetz, of the California Institute of Technology, and Berna Sozen, of Yale University.

Apart from the controversy that broke out in June and as he told Science Media Center Lluís Montoliu, researcher at the National Center for Biotechnology (CNB-CSIC)It is preferable to stick to the substance, as several laboratories have succeeded in generating artificial human embryos. (JO)