World first: Human embryo model grows its own organs – in the lab

Chinese researchers have taken a big step toward a world in which we can cultivate organs for transplant, with the first-ever embryo-disc model that can support and grow the seed cells required for in vitro cultivation. It's also a huge leap for regenerative medicine.

It may sound like science fiction, but researchers have spent years trying to solve this puzzle; stem cells are challenging to control in the complex way needed for artificial organ development, which has been just one of the many obstacles facing this biotechnology.

Apart from the science, one of the hurdles has, of course, been ethical. There are international guidelines that block the culturing of human embryos beyond 14 days post-fertilization – when gastrulation takes place.

Gastrulation is an early but crucial development stage in mammals (and other animals), when an embryo transforms from a one-dimensional layer of epithelial cells into a multilayered, multidimensional form known as the gastrula. The result is a three-layered organism composed of endoderm, mesoderm and ectoderm tissue.

"Gastrulation is when the body's basic architecture is established, transforming the embryo from a flat disc into a three-dimensional structure," says Yu Leqian, corresponding author of the study and a professor at the Institute of Zoology, Chinese Academy of Sciences.

Essentially, this transition marks the point where our cells are set up with the precursors required for organ formation, one of the most critical events in human development.

Because of this, lab-grown embryo-styled models are the only way we can study this developmental window, which takes place between 14 and 21 days. But until now, embryo models have not been able to replicate nature. There's a reason gastrulation is constantly referred to as the "black box" of embryology.

Yu adds that previous human embryo models only generated certain cell types and also failed to produce the "primitive streak" – a groove that facilitates the pathway to this developmental stage. Because of this, cells develop randomly and uncontrollably, deviating from anything that mirrors human development.

While not the same, the difficulty in directing lab-cultivated pluripotent cells to order themselves like nature has also been a challenge in neuroscience research and our efforts to properly unpack the brain's function.

In this new study, the team turned to spatial biology, an emerging field of science that uses precision positioning – in this case, of early human cells – to most accurately recreate nature.

This, in turn, enabled organ-seed cells to grow.

As a result, the scientists created embryonic models – which they called "disc-Gastruloids" – that were able to enter gastrulation and form primitive-streak-like structures. This is something that no other lab models have been able to achieve.

Then, because this critical development stage was achieved, the scientists witnessed cell migration across the disc's surface – again, something seen in human embryo growth.

In the study, more than 80% of the bio-engineered models replicated these developmental processes with success. And the scientists watched as their disc-Gastruloids developed neural tubes, a primitive gut with lung, liver and pancreas progenitors and a primitive heart chamber that rhythmically contracted on its own.

Further single-cell analysis confirmed that the models mirrored the cellular makeup of a 21-day-old human embryo.

"The study has laid the foundation for the ultimate goal of large-scale, modular production of organ-seed cells in vitro to support organ manufacturing and regenerative medicine – potentially enabling tissue repair or even the construction of organs in the laboratory," Yu explains.

While we're still a fair way from cultivated human organs grown from lab embryos, this study potentially speeds up the timeline. It also gives other scientists crucial information for being able to engineer their own embryo models in the lab.

The research was published in the journal Cell.

Source: Institute of Zoology, Chinese Academy of Sciences and China Daily