It’s not easy to watch the brain at work. To understand how it works and what changes lead to disease, you need to be able to observe its cell networks up close. Scientists led by Su-Chun Zhang from the University of Wisconsin-Madison now want to make this easier with a new 3D printing process. With this method, the living brain cells are not stacked vertically in many layers, but are placed horizontally next to each other and in just a few layers, embedded in a transparent biogel.
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In this way, the researchers rebuilt various networks that are often arranged one above the other in the brain, folded to the side at 90 degrees, making them easier to examine. As Zhang’s team writes in the journal “Cell Stem Cell”, the nerve cells made connections with each other and communicated with each other across these synapses using messenger substances.
Such networks do not print well vertically, says Zhang. Then the supporting gel must be firmer so that the cell layers do not slip. In firmer gels, however, the cells cannot grow together well to form connections. The horizontally printed cells, on the other hand, made contact with all neighbors in the softer gel, both laterally as well as up and down. The thin print thickness allows for a good supply of nutrients and oxygen. “We can also measure the electrical activity of the nerve cells as well as the release and uptake of transmitters,” says Zhang.
Different types of brain tissue from the 3D printer
The big advantage of the new method is that the cells can be arranged very precisely and in a controlled manner. According to the scientists, different types of brain tissue can be put together in order to study, for example, brain growth, signal transmission between cells in Down syndrome or the interactions between healthy tissue and neighboring tissue affected by Alzheimer’s. It is also possible to print test tissue for new drug candidates.
Zhang’s team printed a section of the brain that spanned two brain regions: the outer cerebral cortex (cortex), in which voluntary movements and speech arise, and the underlying circuit region called the striatum. Both have their own types of nerve cells. The special thing about their communication is that it always only takes place in one direction, namely from the cortex to the striatum. This is exactly what the researchers observed in their printed brain tissue. “It was pretty amazing. We just put these two types of tissue next to each other, and yet they know how to talk to each other,” says Zhang.
Researcher Yuanwei Yan works in the Zhang lab at the University of Wisconsin-Madison, where researchers have developed a new method for 3D printing brain tissue.
(Bild: Xueyan Li)
In a tissue model for the so-called Alexander disease, in which certain nerve pathways are gradually destroyed, the cells showed the same defective functions as their diseased relatives in the brain.
Comparison to brain organoids
So-called brain organoids have often been used for such studies. These are brain tissues grown in the laboratory that are created from very versatile stem cells. “The advantage of organoids is that they organize themselves, just like it happens in the natural brain,” says Zhang. “The disadvantage is that the development and maturation of the stem cells takes a very long time.” In addition, you have no influence on which networks and circuits are created.
In order to accelerate circuit creation in their manufacturing process, Zhang’s team uses much more advanced and somewhat specialized nerve cell precursors that only have two to four weeks of development time to go. They can also be used to create defined nerve cell types. This not only includes various nerve cells (neurons) that are responsible for information processing, but also – mixed in the right proportions – glial cells, which serve in the brain as tissue support, myelin covering nerve processes and the blood-brain barrier.
(jl)
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