heart. Elefanty is leveraging nature’s navigational
toolbox, whose items have been checked off by the
rigorous oversight of evolution, to make a better
blood cell.THE EMBRYOID PATHWAYcould also be a way forward
for organ replacement.
Writing in Nature in 2018, stem cell pioneer
Martin Pera and colleagues noted that mini brains,
livers and kidneys made from stem cells are pretty
basic, and that maybe we can do better.
“Initiating organ development in an environment
as similar as possible to the developing embryo
might... generate structures that more closely
resemble mature, functional organs, for drug screens
or even for transplantation,” they write.
Usable organs, however, both in terms of
sophistication and size, would need the embryoid
to be pushed much further along the developmental
path than it has been. Elefanty points out two largish
hurdles to that ever happening.
“If you don’t have the right cell type you can’t
make a whole embryo. And secondly, what people
can’t underestimate is the difficulty in reproducingthe environment that is the same as the implanted
embryo,” he says.
Here’s the rub. Fu’s whirling cell clusters
are the right ones to make the headline act of the
embryo, but are missing the supporting entourage:
the trophoblasts that become the placenta, and the
hypoblasts that go on to make the yolk sac, needed to
nourish the early embryo.
These are critical kit in their own right, but they
also play a key role in what is called patterning, which
plots the layout of the body – for example, getting
your liver and spleen in the right spot or crystallising
the geography of the brain’s bumps and folds.
Here, however, the incoming breakers of science
seem relentless.
In 2018, Japanese researchers cultured human
trophoblast stem cells for the first time, raising the
prospect of an artificially grown placenta. Another
announcement last June, however, may have
leapfrogged that altogether.
A group led by Xuefei Gao from the University
of Hong Kong created something called “expanded
potential stem cells”. With some clever chemical
coaxing they heightened the potency of human
embryonic stem cells and iPS cells – stem cells on
steroids if you like. Crucially, expanded potential
stem cells can make those missing bits – the placenta
and yolk sac.
The final step would be replicating implantation,
and in October 2019 the Salk Institute’s Juan
Carlos Izpisua Belmonte led a team that created
expanded potential stem cells from mice, some by
reprogramming cells from the critters’ ears, to make
what they say “could potentially be... fully functional
synthetic embryos in vitro”.
Equipped with placenta and yolk sac, these
are primed to become fully fledged foetuses – and
Belmonte successfully implanted the structures in a
mouse uterus. Only 7% took and, after a week, they
were badly malformed. But it is early days.AS THE SCIENCE RUSHES ONWARDSit is hard enough
to understand it, let alone pass judgment on how far
it should all be allowed to go. There are ground rules
in place. The 14-day rule is as bedrock as ethics gets,
exerting global influence. But, for the purposes of
regulation, is an embryoid an embryo?
In Australia it probably is, even though no one is
pushing the experimental agenda at anywhere near
Fu’s level.
Dianne Nicol is Chair of Australia’s Embryo
Research Licensing Committee, which would make
any such adjudication should the question arise. It
hasn’t – yet. She originally trained as a developmental
biologist and is now a Professor of Law at the
University of Tasmania.ENDODERM (inner layer)alveolar cells thyroid cells digestive cellscardiac muscle digestive muscle tubule cellsred blood cells smooth muscleskin cells neurons pigment cellsMESODERM (middle layer)ECTODERM (outer layer)BCAEXPLAINER FROM LITTLE THINGS, BIG THINGS GROW
CBAAt around
14 days,
epiblast cells
differentiate
into the
endoderm,
ectoderm and
mesoderm,
from which
many different
components of
the body are
developed.
Issue 86 COSMOS – 75STEM CELL FRONTIER