Embryo-like forms derived from skin cells offer a divisive new way of studying human life

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

Two separate teams have found different ways to produce versions of a blastocyst – the stage of development about five days after a sperm fertilizes an egg – possibly opening the door to a major expansion of research.

The scientists make it clear that the models differ from human blastocysts and are incapable of evolving into embryos. But their work comes as new ethical guidelines are drawn up on such research and what could spark new debate.

The teams whose research was published in the journal on Wednesday Nature, believes the models called “blastoids” will help with research on everything from miscarriages to the effects of toxins and drugs on embryos in the early stages.

“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 said in a press release prior to the publication of the research.

Currently, research on the earliest days of embryonic development is based on donated blastocysts from IVF treatment.

The offer is limited, subject to restrictions, and only available to certain research facilities.

Being able to generate unlimited models can therefore be a game changer, said Jose Polo, a professor at Monash University in Australia who led the second research team.

“This ability to work on a scale, we think, will revolutionize our understanding of the early stages of human development,” he said.

The production of blastocyst models has so far only been done in animals, and researchers successfully generated it in 2018 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 of which are derived from human embryos, and others so-called induced pluripotent cells produced from adult cells.

Polo’s team started with mature skin cells instead, but both teams eventually achieved the same result: the cells began to organize themselves into blastoids, with the three key components seen in a human blastosis.

“For us, it was completely amazing that when they are put together, they self-organize, they seem to be talking to each other somehow … and they are consolidating,” Polo said.

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

Both teams’ blastoids eventually contain cells of unknown species, and they have some elements that come specifically from the interaction between a sperm and an egg.

The blastoids worked on average only about 20 percent of the time, although the teams still represent a path to an important research offering.

Ethical debate

The scientists make an effort to make it clear that the models should not be seen as pseudo-embryos and that they cannot develop into fetuses.

Nevertheless, they proceeded cautiously and decided to terminate research with the blastoids four days after culture, equivalent to about ten days after fertilization in a normal egg-sperm interaction.

Research rules regarding human blastocysts set the deadline at 14 days.

Peter Rugg-Gunn, group leader at the Babraham Institute in Bioscience Research in the UK, said the processes are an exciting step forward.

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

“To take advantage of the discovery, the process will have to be more controlled and less changeable,” he said.

And given the differences between the blastoids and human blastocysts, the models offer the ability 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 need to be validated in human embryos,” she said.

The research could also spark ethical debates, say Yi Zheng and Jianping Fu of the University of Michigan’s Department of Mechanical Engineering.

Some “consider research on human blastoids as a path towards the development of human embryos”, they write in an article citing the studies in Nature.

The research “calls for public discussions on the scientific importance of such research, as well as the societal and ethical issues it raises”.

© Agence France-Press

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