Embryo-like shapes extracted from skin cells offer a new divisive way to study human life

Scientists have generated early-stage human embryo models that could help shed light on the “black box” of the early stages of human development and improve research on pregnancy loss and birth defects.

Two separate teams found different ways to produce versions of a blastocyst, the developmental stage around five days after a sperm fertilizes an egg, which could open the door to a vast expansion of research.

The scientists clarify that the models differ from human blastocysts and are not capable of developing into embryos. But their work comes as new ethical guidelines on such research are being drafted and could spark new debate.

The teams, whose research was published Wednesday in the journal NatureThey believe so-called “blastoid” models will aid the investigation of everything from miscarriages to the effects of toxins and drugs on early-stage embryos.

“We are very excited,” said Jun Wu of the University of Texas Southwestern Medical Center, who led one of the teams.

“Studying human development is really difficult, especially at this stage of development, it’s essentially a black box,” he told a news conference before the research was released.

At the moment, research on the early days of embryonic development is based on donated blastocysts from IVF treatment.

But the supply is limited, subject to restrictions, and available only to certain research facilities.

So being able to generate unlimited models could be a game changer, said José Polo, a professor at Australia’s Monash University who led the second research team.

“We believe that this ability to work on a large scale will revolutionize our understanding of the early stages of human development,” he told reporters.

Until now, the generation of blastocyst models has only been done in animals, and researchers in 2018 successfully generated them in mice using stem cells.

The two teams approached the development of a human model in slightly different ways.

Wu’s team used two different types of stem cells, some derived from human embryos and others called induced pluripotent cells produced from adult cells.

Instead, Polo’s team started with adult skin cells, but both teams effectively ended up with the same result: The cells began to organize into blastoids, with the three key components seen in a human blastocyst.

“What was completely surprising to us was that when we put them together, they self-organize, they seem to talk in some way … and they consolidate,” Polo said.

But while the models are similar to human blastocysts in many ways, there are also significant differences.

Both teams’ blastoids ended up containing cells of unknown types and lacking some elements that come specifically from the interaction between a sperm and an egg.

The blastoids only worked about 20 percent of the time on average, although the teams say it still represents a path to a significant research source.

Ethical debate

Scientists strive to make clear that models should not look like pseudo embryos and are not capable of developing into fetuses.

Still, they proceeded cautiously, opting to end the blastoid research four days after culture, which equates to about 10 days after fertilization in a normal egg-sperm interaction.

Research rules involving human blastocysts establish that timeframe at 14 days.

Peter Rugg-Gunn, group leader at the Babraham Institute for Life Sciences Research in the UK, said the processes represent “an exciting development”.

But Rugg-Gunn, who was not involved in the research, said work was needed to improve the current comparatively low success rate of blastoid generation.

“To capitalize on the discovery, the process will need to be more controlled and less variable,” he said.

And given the differences between human blastoids and blastocysts, the models offer the potential to help but not replace research done on donations, said Teresa Rayon of the Francis Crick Institute, a biomedical research center.

They “can help generate hypotheses that will need to be validated in human embryos,” he said.

The research may also spark ethical debates, said Yi Zheng and Jianping Fu of the department of mechanical engineering at the University of Michigan.

Some “might view research on human blastoids as a path to human embryo engineering,” they wrote in a paper accompanying the studies in Nature.

The research “requires public conversations about the scientific importance of such research, as well as the social and ethical issues it raises.”

© Agence France-Presse


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