Researchers from the University of Cambridge have laid the foundations for growing synthetic embryos that could develop a beating heart, gut and brain.
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.
For a human embryo (and its organs) to develop successfully, there needs to be a “dialogue” between these three types of stem 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.
This article originally appeared on Big Think, home of the brightest minds and biggest ideas of all time.
A new study provides key insights in what causes Alzheimer's: a breakdown in the brain’s system for clearing waste.
A new study provides key insights into what’s causing the disease. The research, published in Nature Communications, points to a breakdown over time in the brain’s system for clearing waste, an issue that seems to happen in some people as they get older.
Michael Glickman, a biologist at Technion – Israel Institute of Technology, helped lead this research. I asked him to tell me about his approach to studying how this breakdown occurs in the brain, and how he tested a treatment that has potential to fix the problem at its earliest stages.
Dr. Michael Glickman is internationally renowned for his research on the ubiquitin-proteasome system (UPS), the brain's system for clearing the waste that is involved in diseases such as Huntington's, Alzheimer's, and Parkinson's. He is the head of the Lab for Protein Characterization in the Faculty of Biology at the Technion – Israel Institute of Technology. In the lab, Michael and his team focus on protein recycling and the ubiquitin-proteasome system, which protects against serious diseases like Alzheimer’s, Parkinson’s, cystic fibrosis, and diabetes. After earning his PhD at the University of California at Berkeley in 1994, Michael joined the Technion as a Senior Lecturer in 1998 and has served as a full professor since 2009.
Dr. Michael Glickman