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New embryo models offer hope for research on miscarriages, birth defects
TOKYO, March 18, 2021 (BSS/AFP) – Scientists have generated early-stage
human embryo models that could help shed light on the “black box” of initial
human development stages and improve research on pregnancy loss and birth
defects.
Two separate teams found different ways to produce versions of a
blastocyst — the pre-embryonic mass of cells at the stage of development
around five days after a sperm fertilises an egg — potentially opening the
door for a huge expansion of research.
The scientists make clear 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 fresh
debate.
The teams, whose research was published Wednesday in the journal Nature,
believe the models dubbed “blastoids” will aid research on everything from
miscarriages to the effects of toxins and drugs on early-stage embryos.
“We’re very excited,” said Jun Wu of the University of Texas Southwestern
Medical Centre, 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 press briefing ahead
of the research’s publication.
At the moment, research on the earliest days of embryonic development
relies on donated blastocysts from IVF treatment.
But 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
Jose Polo, a professor at Australia’s Monash University, who led the second
research team.
“This capacity to work at scale, we think, will revolutionise our
understanding of early stages of human development,” he told reporters.
Generating models of blastocysts has so far only been done in animals,
with researchers in 2018 successfully generating 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 other so-called induced pluripotent stem cells, which have the
potential to become any cell and are produced from adult tissue.
Polo’s team instead started with adult skin cells, but both teams ended up
with effectively the same result: the cells began to organise themselves into
blastoids, featuring the three key components seen in a human blastocyst.
“For us what was completely surprising was that when you put them
together, they self-organise, they seem to talk to each other 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 they
lack some elements that come specifically from the interaction between a
sperm and an egg.
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The blastoids only worked about 20 percent of the time on average, though
the teams say that still represents a pathway to a significant research
supply.
– Ethical debate –
The scientists are at pains to make clear that the models should not be
seen as pseudo-embryos, and are not capable of developing into foetuses.
Still, they proceeded cautiously, opting to end research with the
blastoids at four days after cultivation, equivalent to about 10 days after
fertilisation in a normal egg-sperm interaction.
Research rules involving human blastocysts set that deadline at 14 days.
Peter Rugg-Gunn, group leader at the life sciences research Babraham
Institute in the UK, said the processes represented “an exciting advance” but
work was needed to generate the blastoids more reliably.
“To capitalise on the discovery, the process will need to be more
controlled and less variable,” he said.
And given the differences between the blastoids and human blastocysts, any
hypotheses they help generate “will need to be validated in human embryos”,
said Teresa Rayon of the Francis Crick Institute, a biomedical research
centre.
The research may also spark ethical debates, said Yi Zheng and Jianping Fu
of the University of Michigan’s department of mechanical engineering.
“As protocols are optimised, these blastoids will more closely mimic human
blastocysts,” they wrote in an opinion piece published in Nature.
Some “might view human blastoid research as a path towards engineering
human embryos”, they warned.
The research “calls for public conversations on the scientific
significance of such research, as well as on the societal and ethical issues
it raises”.
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