A new embryo-like model could help scientists study the ‘black box’ of early human development

Researchers have developed the first-ever embryo-like model from human embryonic stem cells, a workaround that will let them examine birth defects and diseases they couldn’t otherwise, given ethical and technical issues with studying a human embryo in the lab.

The model resembles a human embryo around 18 to 21 days old — complete with the layers of the cells that will eventually form the nervous system, muscles, the gut, and other cells and structures in the human body. It offers far more insights into the organization and decision-making processes of early-stage embryos than other models, but experts caution it still differs from human embryos in key ways. 

Until now, researchers had often called this early stage of development a “black box,” because of longstanding legal and ethical restrictions on researching embryos that have been developing for more than 14 days, a limit based on the time period after which an embryo can no longer split into identical twins. The “black box” period is when many birth defects and other genetic diseases develop.  

“My hope is that this is a tool that people can use to begin to understand the human-specific features of this time-point in development that we haven’t been able to access,” said Naomi Moris, a research fellow at the University of Cambridge’s Department of Genetics and first author of the publication.

The researchers leading this new study have experience with making 3D models of this stage of development. The same research group published an article in Development in 2014 and an article in Nature in 2018 detailing a similar model derived from mouse embryonic stem cells. But the mouse and the human develop differently. For example, it only takes a mouse 20 to 30 days to develop, a huge difference between the nine months it takes for a human.

Janet Rossant, a senior scientist in the developmental and stem cell biology program at the Hospital for Sick Children, who was not involved in the paper, said the research was an important, incremental step to understanding how humans develop. She was mesmerized by how the cells were able to form the embryo-like model with little guidance.

“They start with a little ball of … unspecialized cells and add specific growth factors that transform them,” she said. “What’s really incredible is that adding those factors allows a ball of cells to self-organize into this [developmental structure] without having to do much else. This is probably close to what actually happens in the embryo itself,” she told STAT. 

But both Moris and Rossant emphasized that this model is not a perfect replica of a real embryo, which limits its potential to fully capture what’s happening to an embryo at this stage in a mother’s womb.

“These [3D models] do not have any developing brain structures or other tissues seen in images of real human embryos,” Rossant said. “Also, importantly, these are not true artificial embryos because they could never survive in the womb. They lack all the cell types to make a placenta.”

Even with its drawbacks, Moris is still excited to see what insight we can gain into exactly how the human embryo uniquely develops. 

“It’s such a cool process to go from a single fertilized egg cell, just one cell, and you end up with something that is, functionally, a whole human being. And, that process kind of happens without us knowing a lot about it. It happens inside a mother’s womb where we don’t necessarily see the process going on,” she said. “How does that actually happen? How does that work?”