Because stem cells have the ability to transform into many different types of cells during the body’s early development, embryonic stem cell research offers unique insights into how an organism grows from a single cell. For the first time, scientists have now been able to create a mouse embryo entirely artificially.

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Researchers have modeled a mouse embryo, here shown at 72 hours, using exclusively stem cells.
Image credit: Berna Sozen-Kaya, Zernicka-Goetz Laboratory, University of Cambridge

Stem cells are crucial for the development of living organisms. At the very beginnings of an embryo, these cells will form the entire organism, including the cells that form the body’s vital organs and tissues, such as the heart, lungs, and skin.

During its first 3 to 5 days, the human or mammalian embryo is called a blastocyst. The blastocyst is made up of embryonic stem cells (ESCs) that are generated by the egg after it has been fertilized by a sperm.

The blastocyst also contains trophoblast stem cells (TSCs), which will create the placenta, and primitive endoderm stem cells that will form the yolk sac – a membranous sac that provides nutrients to the developing embryo and forms before the placenta.

Researchers from the University of Cambridge in the United Kingdom, led by Prof. Magdalena Zernicka-Goetz from the Department of Physiology, Development, and Neuroscience, set out to genetically create a structure resembling a mouse embryo using exclusively ESCs and TSCs. The study was published in the journal Science.

Prof. Zernicka-Goetz and team used genetically modified ESCs and TSCs, as well as a 3-D extracellular matrix (ECM) – a noncellular component found in all tissues and organs that functions as a scaffolding for cells, and facilitates biochemical reactions that help cells to differentiate and morph into other organs and tissues.

Researchers found that the ESCs, TSCs, and the 3-D ECM “communicated” with each other and organized themselves into a self-assembling structure that had the properties of a natural embryo.

Prof. Zernicka-Goetz explains the findings:

“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. It has anatomically correct regions that develop in the right place and at the right time […] 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. Without this partnership, the correct development of shape and form and the timely activity of key biological mechanisms does not take place properly.”

The creation of this artificial embryo-like structure facilitated insights into the development process of a natural embryo. Prof. Zernicka-Goetz and her colleagues were able to see that the artificial embryo followed the same pattern as a natural one, whereby stem cells organize themselves into creating the pro-amniotic cavity that will later host the embryo.

These insights are key to understanding the early stages of human development as well, as Dr. Andrew Chisholm – head of Cellular and Developmental Science at the Wellcome Trust – explains:

“This is an elegant study creating a mouse embryo in culture that gives us a glimpse into the very earliest stages of mammalian development,” Dr. Chisholm says. “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 and health.”

The Wellcome Trust and the European Research Council were the main funding bodies behind this research project.

Prof. Zernicka-Goetz has also worked on other projects which, together with this one, help advance the field of human embryo research. She recently achieved another breakthrough, by developing human embryos in vitro beyond the implantation stage for the first time. Prof. Zernicka-Goetz hopes that her research will help scientists to overcome one of the main obstacles in human embryo research: the insufficient number of embryos available.

“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. 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 goes wrong.”

Prof. Magdalena Zernicka-Goetz

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