Scientists have developed early stage human embryo models that can help shed light on the “black box” of the initial human development stages and improve research on pregnancy loss and birth defects.
Two separate teams have found different ways to produce versions of a blastocyst – the developmental stage about five days after a sperm fertilizes an egg – potentially opening the door for a massive expansion of research.
The scientists make it clear that the models are different from human blastocysts and are incapable of developing into embryos. But their work comes as new ethical guidelines for such research are established and this could spark new discussions.
The teams, whose research was published Wednesday in the journal Nature, think the models called “blastoids” will support research on 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 very difficult, especially at this stage of development it is essentially a black box,” he told a press conference prior to the publication of the study.
Currently, research into the first days of embryonic development relies on donated blastocysts from IVF treatment.
However, the offer is limited, subject to restrictions and only available for certain research facilities.
So it could be a game-changer to generate unlimited models, said Jose Polo, a professor at Monash University in Australia who led the second research team.
“This ability to operate at scale, we believe, will revolutionize our understanding of early stages of human development,” he told reporters.
The generation of blastocyst models has so far 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 so-called induced pluripotent cells produced from adult cells.
Polo’s team started with adult skin cells instead, but both teams ended up with basically the same result: The cells started organizing themselves into blastoids, with the three main components seen in a human blastocyst.
“What was completely surprising to us was that when you put them together, they organize themselves, they somehow seem to talk to each other… and they consolidate,” said Polo.
But while the models resemble human blastocysts in many ways, there are also significant differences.
Both teams’ blastoids eventually contain cells of unknown types, and they lack 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, though the teams say this is still a path to significant research offering.
Ethical debate
The scientists are doing their best to make it clear that the models should not be viewed as pseudo-embryos and are incapable of developing into fetuses.
Still, they proceeded with caution and chose to end the blastoid study four days after cultivation, which corresponds to approximately 10 days after fertilization in a normal egg-sperm interaction.
Research rules regarding human blastocysts set that deadline to 14 days.
Peter Rugg-Gunn, group leader at the Babraham Institute of Life Sciences in the UK, said the processes were “exciting progress”.
But Rugg-Gunn, who was not involved in the study, said work was needed to improve the current relatively low success rate in generating the blastoids.
“To take advantage of the discovery, the process will have to be more controlled and less variable,” he said.
And given the differences between the blastoids and human blastocysts, the models offer the potential to aid, but not replace, donation research, said Teresa Rayon of the Francis Crick Institute, a biomedical research center.
They “can help develop hypotheses to be validated in human embryos,” she said.
The research could also give rise to ethical debates, say Yi Zheng and Jianping Fu of the University of Michigan’s mechanical engineering department.
Some “might view human blastoid research as a path to human embryo development,” they wrote in an article accompanying the studies in Nature
The research “calls for public discussion about the scientific significance of such research, as well as the societal and ethical issues it raises”.
© Agence France-Presse