Yuanwei Yan is a scientist in the Zhang lab at UW–Madison, where researchers have developed new printing methods to grow brain tissues for use in the study of neurodevelopmental disorders like Alzheimer’s and Parkinson’s diseases. [Photo courtesy of UW-Madison/Xuey]
The team said their research has important implications for scientists studying the brain and developing treatments for neurological and neurodevelopmental disorders like Alzheimer’s and Parkinson’s.
“This could be a hugely powerful model to help us understand how brain cells and parts of the brain communicate in humans,” said Su-Chun Zhang, professor of neuroscience at the UW School of Medicine and Public Health and a member of UW–Madison’s Waisman Center. “It could change the way we look at stem cell biology, neuroscience and the pathogenesis of many neurological and psychiatric disorders.”
Zhang and Yuanwei Yan, a scientist in the lab, say printing methods limited previous attempts to print brain tissue. Instead of using traditional approaches, which stack layers vertically, the researchers did so horizontally. The researchers equated this to pencils laid next to one another on a tabletop. They placed brain cells (neurons grown from induced pluripotent stem cells) in a soft “bio-ink” gel.
According to Yan, the tissue stays relatively thin and makes it easy for neurons to get necessary oxygen and nutrients from the growth media.
“The tissue still has enough structure to hold together but it is soft enough to allow the neurons to grow into each other and start talking to each other,” Zhang said.
The team says the printed cells reach through the medium to form connections inside each printed layer and across layers, forming networks comparable to human brains. Effectively, they can “speak” to each other. The neurons communicate, send signals, interact through neurotransmitters and work with support cells added to the printed tissue.
Zhang said they printed the cerebral cortex and the striatum and found that, even when the team printed different cells from different areas of the brain, they still managed to establish connections in a specific way. The team believes its technique offers precision not found in brain organoids as well. This produces a specificity that in turn provides flexibility.
“Our lab is very special in that we are able to produce pretty much any type of neurons at any time. Then we can piece them together at almost any time and in whatever way we like,” Zhang says. “Because we can print the tissue by design, we can have a defined system to look at how our human brain network operates. We can look very specifically at how the nerve cells talk to each other under certain conditions because we can print exactly what we want.”
The printed brain tissue could now be used to study signaling between cells in Down syndrome, interactions between healthy tissue and neighboring tissue affected by Alzheimer’s, testing new drug candidates or even watching the brain grow.
Zhang’s team said its new printing technique should be accessible to many labs and doesn’t require special bio-printing equipment or culturing methods. Researchers can study it in depth with microscopes, standard imaging techniques and commonly used electrodes.
Next, the researchers want to look at specialization, improving their bio-ink and refining equipment for specific cell orientation within printed tissue.
“Right now, our printer is a benchtop commercialized one,” Yan said. “We can make some specialized improvements to help us print specific types of brain tissue on-demand.”
For more on this 3D printing method, see the team’s publication in the journal Cell Stem Cell.
