Inside a lab at the Sanford Consortium for Regenerative Medicine, researchers are doing something truly remarkable. They are growing tiny versions of developing human brains in order to study everything from Alzheimer’s disease to the Zika virus. Alysson Muotri is the co-director of the UC San Diego Stem Cell Program and leads the team researching brain organoids. He recently sat down with Dr. David Granet on Health Matters to discuss the endless possibilities of his research.
Muotri’s organoids are often referred to as “mini-brains,” but they are far from what that name might suggest. The organoids are grown from stem cells, which are harvested from living tissue, such as skin cells. Researchers give those stem cells instructions to become neural cells. Eventually they form tiny clusters of neural cells, about the size of a pea. Those clusters have been shown to exhibit some of the same characteristics of developing human brains, including firing electrical signals in specific patterns. But, the organoids do not contain every type of brain tissue, and have no vascularization.
Despite the differences with the human brain, organoids have proven useful in understanding and treating disease. One of the major successes of Muotri’s research was finding and testing an existing drug to treat mothers infected with Zika virus. The drug can prevent the disease from being passed to the baby and causing microcephaly. Muotri is hoping his lab will continue to have success using the organoids as an effective brain model to find more cures, and provide a deeper understanding of brain development and disease. And, his work isn’t limited to Earth. Muotri recently launched his organoids into space for a groundbreaking study.
Watch — Using Stem Cells to Research the Brain – Health Matters
Transplants are expensive and risky, and donor organs are in short supply. Researchers at UC San Diego are working on technology to change all of that. It’s called bioprinting. In simple terms, bioprinting is 3D printing with living tissue. Researcher Shaochen Chen has been perfecting the process in his lab for years.
Bioprinting is a complex process that takes place in a matter of seconds right before your eyes. Chen’s lab builds their own printing machines, which shine light into a gel the team has developed. Any spot the light hits becomes solid. Because the process uses light, it allows the team to recreate microscopic structures like liver cells or vascular networks with incredible precision.
While the process enables researchers to accurately reproduce biological structures, it’s what’s inside the gel that makes bioprinting truly remarkable. The gel can be filled with stem cells from a potential transplant recipient. Those cells can fuse with tissue in the body as the gel disintegrates, essentially repairing damage with the patient’s own cells. Chen’s lab has shown the process can work in rats with severe spinal cord injuries. Someday, the process could be used in humans to do the same.
Bioprinting is also helpful to researchers in other fields. Chen has teamed up with Alysson Muotri and Karl Wahlin to help them study the connection between the eye and the brain. Their labs are conducting research using organoids – tiny organ-like structures grown from stem cells. They realized in order to effectively study how brain and retinal organoids interact with one another, they need to physically separate them at just the right distance, similar to how they might be separated in the womb. Chen’s lab developed a bioprinted structure to achieve that separation, taking the partnership to the next level.
Watch — 3D Printing with Stem Cells – Shaochen Chen
It sounds like the plot of a science fiction movie. Scientists grow brains in a lab and use them to power robots. But, it’s really happening at UC San Diego – to a degree. Stem cell researcher Alysson Muotri has teamed up with a high school student for the groundbreaking project. It’s called the Neurobot, and it’s really cool.
It all started thanks to a high school student with a lot of talent and initiative. Christopher Caligiuri read about the work the Muotri lab was doing with brain organoids and wanted to get involved. He reached out and said he would love to help, and had some experience in robotics if that was useful. Muotri not only agreed, he put the sophomore on a pretty impressive project.
To understand how the Neurobot works, you have to understand the basics of the Muotri lab’s brain organoid research. Brain organoids are clusters of brain cells grown in the lab from human stem cells. They don’t contain every type of brain cell, nor do they have the all the various structures of full-fledged brains. They certainly aren’t capable of independent thought. But, they do give off electrical signals, similar to those of a developing fetus.
The team is using those signals to control the Neurobot. Researchers in the Muotri lab collect and record signal data from the organoids. That data is then fed into the robot through software Caligiuri developed. The software interprets the data as a speed commands, which control how fast the Neurobot walks. If you think it sounds cool, you have to see it in action.
Watch — Neurobot: Robotics Meets Stem Cells
There are a number of diseases that can lead to blindness. But, a researcher at UC San Diego thinks there might be one way to cure them all. It’s called endogenous regeneration. Think of a lizard re-growing a lost tail. Zebrafish can do something similar with retinal tissue. Researcher Karl Wahlin says there is evidence humans have the potential to do the same, if scientists can figure out how to activate the process.
Wahlin’s work isn’t limited to teaching the body to repair itself. He’s also using stem cells to study different eye diseases and search for cures. He works with what are known as retinal organoids – miniature retinal models grown in the lab. These can be made from stem cells of people with specific eye diseases so researchers can see how those diseases might develop in the womb, and which treatments might be effective against them.
Now, Wahlin is teaming up with Alysson Muotri from the UC San Diego Stem Cell program who uses brain organoids for similar research. The two have begun working together with the help of a bioengineer who builds 3D-printing machines that can incorporate stem cells. Learn how it all works in the latest piece from the Building the Brain Series.
Watch — Stem Cells and Curing Blindness – Karl Wahlin
Inside of each brain, there is the possibility to understand how trillions of neural connections come to sense the world, record memories, create an individual, and shape who you are and who you will become. Can we ever learn how this happens?
By using cortical organoids – self organized clusters of neurons generated by stem cells, that is what Alysson Muotri’s lab at the Sanford Consortium for regenerative medicine wants to learn.
Called “brain organoids” because they exhibit many of the characteristics of a developing brain they are asking what happens to build a brain? What happens to create a human mind, and who we are? How does this process become disordered, giving rise to conditions like autism, schizophrenia, epilepsy, and degeneration? And how can they find ways to intervene and rescue the mind from disorders, and even restore lost function?
Muotri’s lab and a host of collaborators in and out of UC San Diego are using a diverse array of methods and tools on these brain organoids, from researching the details of vision to how neurons connect and form networks, to engineering ways to help the organoids become more complex, to the differences between normal brains and brains with cognitive disorders, even to growing brain organoids in space to understand causes of autism and Alzheimer’s disease.
Join Alysson Muotri, Director of the UC San Diego Stem Cell Program as he takes you on a journey to visit the labs and collaborators who are exploring how a brain is built on Building the Brain.
Watch — Building The Brain With Alysson Muotri