Scientists in Europe have created embryonic-like structures that mimic a crucial yet enigmatic stage of human development.
The structures, created by stem cells and called gastruloids, are the first to form a 3D unit that describes how the body will take shape. The gastruloids developed rudimentary components of a heart and nervous system, but lacked the components to form a brain and other cell types that would make them capable of becoming a viable fetus.
Researchers are creating increasingly sophisticated artificial structures to study embryonic development in the lab. The latest method for making these structures, published in Nature today1
The model can help researchers understand the role of genetics and environmental factors in such disorders, says Fu Jianping, a bioengineer at the University of Michigan in Ann Arbor. “It’s on the horizon now.”
The artificial structures make it possible to avoid ethical problems with research on human embryos. But as the structures become more advanced and life-like, they can also push ethical boundaries, say researchers.
Human embryos make a significant leap during their third week, when the largely homogeneous ball of cells begins to differentiate and develop specific characteristics of the body parts they will become, a process known as gastrulation. During this process, the embryo lengthens and establishes a body plan with a head and tail, often called the head-to-tail axis.
But scientists have never seen this process in action. This is partly because many countries have regulations that prevent embryos from growing in the research laboratory after 14 days after conception.
Over the past year, several research groups have cultivated embryonic stem cell structures that model when cells begin to differentiate. The latest model, developed by Naomi Moris and Alfonso Martinez Arias, developmental biologists at the University of Cambridge, United Kingdom and their colleagues in the Netherlands, is the first to show what happens when the plan for body development is planned, about 18-21 days after conception.
“This important discovery will help us understand the critical mechanisms of human body planning,” said Li Tianqing, a developmental biologist at the Institute of Primate Translational Medicine in Yunnan, China, who also works with embryonic-like structures.
Moris says the most exciting result was the formation of pockets of cells that extend symmetrically from head to tail. Genetic analysis showed that the cells were the ones that would eventually continue to form muscle in the trunk, spine, heart and other organs.
Moris says the embryo model will help researchers study how the cell pattern appears and where it might go wrong. Many diseases are caused by errors in this process, including scoliosis, which causes curvature of the spine. “This is a new system that opens up a whole host of issues,” she says.
The team used their experience in creating gastruloids from embryonic stem cells from mice over the past five years to develop human cell structures.
It took the team two years to figure out the right conditions, says Arias. These include starting with a compact colony of about 400 cells. Significant progress was made in treating them with a chemical called Chiron that accelerated their development. The researchers then separated the cells and put them in a well.
If everything is done properly, the cells develop into 3D structures on their own – and then spontaneously mimic the gastrulation process, says Moris, who has since made hundreds of human gastruloids and says they work almost 70% of the time. “It’s a really simple process, because the cells themselves do the hard work,” she says.
Although they show some key functions of a 21-day-old embryo, the gastruloids reach that stage after only 72 hours and do not survive for more than four days before collapsing on their own, says Moris.
Researchers will probably use the model to create structures that are even more realistic representations of early development, says Fu. Over the next 5-10 years, they may be able to add cells that would continue to mimic the placenta. He also expects to see gastruloids with throbbing hearts. In the womb, the heart of an embryo starts beating for about 22 days. And although the structures have not yet developed the components of brain development, Arias believes that blocking a certain molecular signal may allow a rudimentary organ to grow.
Such experiments will push ethical boundaries and ask questions about whether these structures can develop into viable fetuses. “We have to be careful not to start creating human embryos,” says Fu.
Arias agrees that this would be a ruthless goal. But could it be done? “Not in the short term,” he says.