pregnancy (photo by vecteezy)
A “synthetic” fetus with a brain and a beating heart, created by an international team of scientists, could be the first step in understanding why some pregnancies fail.
The fetus includes the basics of all the body’s organs, including neural tubes and intestines that protect the spine and the developing intestines. The first creation in the world can also solve the crisis of the shortage of organ donors. The team from the University of Cambridge and Caltech say the embryos may guide the repair and development of synthetic human organs.
Researchers used a combination of stem cells from mice without fertilized eggs or sperm. “Our mouse embryo model not only develops a brain, but also a beating heart, all the components that make up the body,” says lead author Professor Magdalena Zarnica-Gutz in a press release.
“It’s just unbelievable that we’ve come this far. This has been the dream of our community for years, and the main focus of our work for a decade, and we’ve finally done it.”
The fetus began to grow muscles, intestines and nervous system, shedding new light on the way tissues are formed and the causes of genetic diseases. Successful pregnancies need a “dialogue” between fetus and mother. In the first week after fertilization, three types of stem cells develop.
One of them will eventually become the tissues of the body. The others support the development of the fetus. They become the placenta, which connects the fetus to the mother and provides oxygen and nutrients, and the yolk sac, where the fetus receives its nutrients and grows.
Each group needs to send mechanical and chemical signals to each other, telling the embryo how to develop properly. Prof. Zarnica-Getz points out that so many pregnancies fail at this stage, before most women realize they are pregnant.
“This early period is the foundation for everything else after pregnancy,” Zarnicka-Getz says. “If it goes wrong, the pregnancy will fail.”
The researchers mimicked natural processes in the lab by guiding three types of stem cells found in early mammalian development to the point where they begin to interact. Inducing the expression of a certain set of genes and establishing a unique environment caused them to “talk” to each other.
The model copies the stages of natural mouse embryo development that occur up to eight and a half days after fertilization. Over the past decade, Prof. Zarnicka-Gutz’s group has been studying these initial stages in order to understand why pregnancy sometimes goes wrong.
“The stem cell embryo model is important because it gives us access to the developing structure at a stage that is usually hidden from us due to the implantation of the tiny embryo in the mother’s womb,” explains the author of the study. “This approach allows us to manipulate genes to understand their developmental roles in a model experimental system.”
The study authors ignited development of their synthetic embryo by weaving different cultured stem cells. They represented each of the three tissue types in the right proportions and environment to promote growth and communication. After self-assembly into the embryo, the researchers discovered that they signaled chemically, mechanistically and through touch.
“This period of human life is so mysterious, to be able to see how it happens in a plate – to have access to these individual stem cells, to understand why so many pregnancies fail and how we can prevent that from happening” is pretty special, Zarnicka-Gutz adds “We looked at the dialogue that needs to happen between the different types of stem cells at that time – we showed how it happens and how it can go wrong.”
A major advance is the ability to create the entire brain, in particular the forebrain – a major goal in the development of synthetic embryos. In Prof. Zarnicka-Gutz’s system, this part requires messages from one of the extra-embryonic tissues in order to develop successfully.
“This opens up new possibilities to study the mechanisms of neural development in an experimental model,” explains Zarnica-Gutz.
“In fact, we demonstrate the proof of this principle in the paper by eliminating a gene that is already known to be essential for the formation of the neural tube, a precursor of the nervous system, and the development of the brain and eye. In the absence of this gene, the synthetic embryos show exactly the same defects in brain development as in an animal carrying this mutation. This means we can begin to apply this type of approach to the many genes with unknown function in brain development.”
The researchers are now developing similar human models with the potential to be targeted to create specific organ types to understand mechanisms behind crucial processes that would otherwise be impossible to study in real embryos.
Currently, UK law only allows human embryos to be studied in the laboratory up to day 14 of development. The findings, published in the journal Nature, may lead to the development of synthetic organs for patients awaiting transplantation.
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“There are so many people around the world who wait years for an organ transplant,” Zarnica-Getz concludes. “What makes our work so exciting is that the knowledge that came out of it can be used to grow the right human synthetic organs to save lives that are currently lost. It should also be possible to influence and heal adult organs by using the knowledge we have about how they are formed.”
The creation of “synthetic” human embryos is outside the legal framework of the UK’s Human Fertilization and Embryology Act. However, it would be illegal to use them to establish a pregnancy in a woman, as they are not classified as “permissible embryos”.
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