Understanding the very early stages of embryo development is of
interest because this knowledge may help explain why more than two out
of three human pregnancies fail at this time.
Scientists at the University of Cambridge have managed to create a
structure resembling a mouse embryo in culture, using two types of stem
cells - the body's 'master cells' - and a 3D scaffold on which they can
‘A structure resembling a mouse embryo in culture, using two types of stem cells, has been created by researchers.’
Once a mammalian egg has been fertilized by a sperm, it divides
multiple times to generate a small, free-floating ball of stem cells.
The particular stem cells that will eventually make the future body, the
embryonic stem cells (ESCs) cluster together inside the embryo towards
one end: this stage of development is known as the blastocyst. The other
two types of stem cell in the blastocyst are the extra-embryonic
trophoblast stem cells (TSCs), which will form the placenta; and
primitive endoderm stem cells that will form the so-called yolk sac,
ensuring that the fetus's organs develop properly and providing
Previous attempts to grow embryo-like structures using only ESCs
have had limited success. This is because early embryo development
requires the different types of cell to coordinate closely with each
However, in a study published today in the journal Science
Cambridge researchers describe how, using a combination of
genetically-modified mouse ESCs and TSCs, together with a 3D scaffold
known as an extracellular matrix, they were able to grow a structure
capable of assembling itself and whose development and architecture very
closely resembled the natural embryo.
"Both the embryonic and extra-embryonic cells start to talk to each
other and become organized into a structure that looks like and behaves
like an embryo," explains Professor Magdalena Zernicka-Goetz from the
Department of Physiology, Development and Neuroscience, who led the
research. "It has anatomically correct regions that develop in the right
place and at the right time."
Professor Zernicka-Goetz and colleagues found a remarkable degree of
communication between the two types of stem cell: in a sense, the cells
are telling each other where in the embryo to place themselves.
"We knew that interactions between the different types of stem cell
are important for development, but the striking thing that our new work
illustrates is that this is a real partnership - these cells truly guide
each other," she says. "Without this partnership, the correct
development of shape and form and the timely activity of key biological
mechanisms doesn't take place properly."
Comparing their artificial 'embryo' to a normally-developing embryo,
the team was able to show that its development followed the same
pattern of development. The stem cells organize themselves, with ESCs at
one end and TSCs at the other. A cavity opens then up within each
cluster before joining together, eventually to become the large,
so-called pro-amniotic cavity in which the embryo will develop.
While this artificial embryo closely resembles the real thing, it is
unlikely that it would develop further into a healthy foetus, say the
researchers. To do so, it would likely need the third form of stem cell,
which would allow the development of the yolk sac, which provides
nourishment for the embryo and within which a network of blood vessel
develops. In addition, the system has not been optimised for the correct
development of the placenta.
Professor Zernicka-Goetz recently developed a technique that allows
blastocysts to develop in vitro beyond the implantation stage, enabling
researchers to analyze for the first time key stages of human embryo
development up to 13 days after fertilization. She believes that this
latest development could help them overcome one of the main barriers to
human embryo research: a shortage of embryos. Currently, embryos are
developed from eggs donated through IVF clinics.
"We think that it will be possible to mimic a lot of the
developmental events occurring before 14 days using human embryonic and
extra-embryonic stem cells using a similar approach to our technique
using mouse stem cells," she says. "We are very optimistic that this
will allow us to study key events of this critical stage of human
development without actually having to work on embryos. Knowing how
development normally occurs will allow us to understand why it so often
The research was largely funded by the Wellcome Trust and the European Research Council.
Dr Andrew Chisholm, Head of Cellular and Developmental Science at
Wellcome, said: "This is an elegant study creating a mouse embryo in
culture that gives us a glimpse into the very earliest stages of
mammalian development. Professor Zernicka-Goetz's work really shows the
importance of basic research in helping us to solve difficult problems
for which we don't have enough evidence for yet. In theory, similar
approaches could one day be used to explore early human development,
shedding light on the role of the maternal environment in birth defects