Researchers 3D-print functional human brain tissue
University of Wisconsin-Madison
It's an achievement with important implications for
scientists studying the brain and working on treatments for a broad range of
neurological and neurodevelopmental disorders, such as Alzheimer's and
Parkinson's disease.
"This could be a hugely powerful model to help us understand how brain cells and parts of the brain communicate in humans," says Su-Chun Zhang, professor of neuroscience and neurology at 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."
Printing methods have limited the success of previous
attempts to print brain tissue, according to Zhang and Yuanwei Yan, a scientist
in Zhang's lab. The group behind the new 3D-printing process described their
method today in the journal Cell Stem Cell.
Instead of using the traditional 3D-printing approach,
stacking layers vertically, the researchers went horizontally. They situated
brain cells, neurons grown from induced pluripotent stem cells, in a softer
"bio-ink" gel than previous attempts had employed.
"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 says.
The cells are laid next to each other like pencils laid
next to each other on a tabletop.
"Our tissue stays relatively thin and this makes it
easy for the neurons to get enough oxygen and enough nutrients from the growth
media," Yan says.
The results speak for themselves -- which is to say, the
cells can speak to each other. The printed cells reach through the medium to
form connections inside each printed layer as well as across layers, forming
networks comparable to human brains. The neurons communicate, send signals,
interact with each other through neurotransmitters, and even form proper
networks with support cells that were added to the printed tissue.
"We printed the cerebral cortex and the striatum and
what we found was quite striking," Zhang says. "Even when we printed
different cells belonging to different parts of the brain, they were still able
to talk to each other in a very special and specific way."
The printing technique offers precision -- control over
the types and arrangement of cells -- not found in brain organoids, miniature
organs used to study brains. The organoids grow with less organization and
control.
"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."
That specificity provides flexibility. The printed brain
tissue could 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.
"In the past, we have often looked at one thing at a
time, which means we often miss some critical components. Our brain operates in
networks. We want to print brain tissue this way because cells do not operate
by themselves. They talk to each other. This is how our brain works and it has
to be studied all together like this to truly understand it," Zhang says.
"Our brain tissue could be used to study almost every major aspect of what
many people at the Waisman Center are working on. It can be used to look at the
molecular mechanisms underlying brain development, human development,
developmental disabilities, neurodegenerative disorders, and more."
The new printing technique should also be accessible to
many labs. It does not require special bio-printing equipment or culturing
methods to keep the tissue healthy, and can be studied in depth with
microscopes, standard imaging techniques and electrodes already common in the
field.
The researchers would like to explore the potential of
specialization, though, further improving their bio-ink and refining their
equipment to allow for specific orientations of cells within their printed
tissue..
"Right now, our printer is a benchtop commercialized
one," Yan says. "We can make some specialized improvements to help us
print specific types of brain tissue on-demand."
This study was supported in part by NIH-NINDS (NS096282,
NS076352, NS086604), NICHD (HD106197, HD090256), the National Medical Research
Council of Singapore (MOH-000212, MOH-000207), Ministry of Education of
Singapore (MOE2018-T2-2-103), Aligning Science Across Parkinson's
(ASAP-000301), the Bleser Family Foundation, and the Busta Foundation.
