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The organoid revolution: From a breast in Jello to a synthetic embryo

Someday, scientists could use stem cells to guide the development of synthetic organs for patients awaiting transplants.
Key Takeaways
  • For over a century, scientists have dreamed of growing human organs, and this dream has almost become a reality with the development of organoids.
  • Organoids are artificially synthesized clumps of cells that function together to mimic the properties of real organs; however, they lack the function and complexity of organs that grow inside an organism.
  • Scientists have developed a more holistic strategy to synthesize organoids, resulting in an embryo-like model that creates heart, gut, and brain tissue.

For over a century, scientists have dreamed of growing human organs sans humans. This technology could put an end to the scarcity of organs for transplants. But that’s just the tip of the iceberg. The capability to grow fully functional organs would revolutionize research. For example, scientists could observe mysterious biological processes, such as how human cells and organs develop a disease and respond (or fail to respond) to medication without involving human subjects. 

Recently, a team of researchers from the University of Cambridge has laid the foundations not just for growing functional organs but functional synthetic embryos capable of developing a beating heart, gut, and brain. Their report was published in Nature.

Natural (top) and synthetic (bottom) embryos side by side to compare brain and heart formation. (Credit: G Amadei et al., Nature, 2022.)

The organoid revolution

In 1981, scientists discovered how to keep stem cells alive. This was a significant breakthrough, as stem cells have notoriously rigorous demands. Nevertheless, stem cells remained a relatively niche research area, mainly because scientists didn’t know how to convince the cells to turn into other cells.

Then, in 1987, scientists embedded isolated stem cells in a gelatinous protein mixture called Matrigel, which simulated the three-dimensional environment of animal tissue. The cells thrived, but they also did something remarkable: they created breast tissue capable of producing milk proteins. This was the first organoid — a clump of cells that behave and function like a real organ. The organoid revolution had begun, and it all started with a boob in Jello.

For the next 20 years, it was rare to find a scientist who identified as an “organoid researcher,” but there were many “stem cell researchers” who wanted to figure out how to turn stem cells into other cells. Eventually, they discovered the signals (called growth factors) that stem cells require to differentiate into other types of cells.

By the end of the 2000s, researchers began combining stem cells, Matrigel, and the newly characterized growth factors to create dozens of organoids, from liver organoids capable of producing the bile salts necessary for digesting fat to brain organoids with components that resemble eyes, the spinal cord, and arguably, the beginnings of sentience.

Synthetic embryos

Organoids possess an intrinsic flaw: they are organ-like. They share some characteristics with real organs, making them powerful tools for research. However, no one has found a way to create an organoid with all the characteristics and functions of a real organ. But Magdalena Żernicka-Goetz, a developmental biologist, might have set the foundation for that discovery.

Żernicka-Goetz hypothesized that organoids fail to develop into fully functional organs because organs develop as a collective. Organoid research often uses embryonic stem cells, which are the cells from which the developing organism is created. However, there are two other types of stem cells in an early embryo: stem cells that become the placenta and those that become the yolk sac (where the embryo grows and gets its nutrients in early development). For a human embryo (and its organs) to develop successfully, there needs to be a “dialogue” between these three types of stem cells. In other words, Żernicka-Goetz suspected the best way to grow a functional organoid was to produce a synthetic embryoid.

As described in the aforementioned Nature paper, Żernicka-Goetz and her team mimicked the embryonic environment by mixing these three types of stem cells from mice. Amazingly, the stem cells self-organized into structures and progressed through the successive developmental stages until they had beating hearts and the foundations of the brain.

“Our mouse embryo model not only develops a brain, but also a beating heart [and] all the components that go on to make up the body,” said Żernicka-Goetz. “It’s just unbelievable that we’ve got this far. This has been the dream of our community for years and major focus of our work for a decade and finally we’ve done it.”

If the methods developed by Żernicka-Goetz’s team are successful with human stem cells, scientists someday could use them to guide the development of synthetic organs for patients awaiting transplants. It also opens the door to studying how embryos develop during pregnancy.


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