The researchers mimicked natural processes in the lab by guiding the three types of stem cells involved in early mammalian development to the point where they begin to interact.
By inducing the expression of a particular set of genes and creating a unique environment for their interactions, they made the stem cells “talk” to each other.
The stem cells then self-organized into structures that progressed through successive stages of development to create beating hearts, the foundations of the brain, and the yolk sac, where the embryo develops and obtains nutrients in its first few weeks.
Our mouse embryo model not only develops a brain, but also a beating heart and all the components that make up the body
Unlike other laboratory embryos, these models managed to get the entire brain – including the anterior part – to start developing, which had never been achieved before.
The team believes that their results, published this Thursday in the journal Naturecould help researchers understand why some embryos fail while others thrive in a healthy pregnancy.
Furthermore, the results could be used to guide the repair and development of ‘synthetic’ human organs for transplantation.
“Our mouse embryo model not only develops a brain, but also a beating heart and all the components that make up the body. It’s amazing that we’ve come this far. This has been the soil of our community for years and the main goal of our work for a decade,” says Zernicka-Goetz, Professor of Mammalian Development and Stem Cell Biology.
For a human embryo to develop successfully there must be “dialogue” between the tissues that will form it and those that will connect it to the mother.
In the first week after fertilization, three types of stem cells develop: one will eventually become the body’s tissues, and the other two support the development of the embryo.
One of these types of extra-embryonic stem cells will become the placenta, which connects the fetus to the mother and provides it with oxygen and nutrients, and the second is the yolk sac, where the embryo grows and gets its nutrients in the early stages of development .
Many pregnancies fail at the point when the three types of stem cells begin to send mechanical and chemical signals to each other, telling the embryo how to develop properly.
For the last decade, Professor Zernicka-Goetz’s group at Cambridge has been studying these early stages of pregnancy, hoping to understand why some pregnancies fail and others succeed.
“The stem cell embryo model is important because it gives us accessibility to the developing structure at a stage that is normally hidden from us due to the implantation of the tiny embryo in the mother’s uterus,” explains Zernicka-Goetz.
To guide the development of their lab embryo, the researchers put together cultured stem cells from each of the three tissue types in the right proportions and environment to promote their growth and communication with one another.
They discovered that the extra-embryonic cells send chemical signals to the embryonic cells, but also mechanical, or through touch, guiding the development of the embryo.
A great advance of the study is the ability to generate the whole brainin particular the anterior part, which until now has been one of the main stumbling blocks in the development of synthetic embryos.
They could also be used to guide the development of laboratory organs for patients awaiting transplants.
In the Zernicka-Goetz system, this works because this part of the brain requires signals from one of the extra-embryonic tissues in order to develop.
“This opens up new possibilities to study the mechanisms of neurodevelopment in an experimental model,” defends Zernicka-Goetz.
Although the current research was done in mouse models, researchers are developing similar human models with the potential to target the generation of specific organ types to understand the mechanisms underlying crucial processes that cannot be studied in real embryos.
Currently, UK law only allows human embryos to be studied in the laboratory up to the 14th day of development.
If in the future the methods developed by this team work with human stem cells, they could also be used to guide the development of laboratory organs for patients awaiting transplants.