Uppsala researchers create 3D-printed human nerve tissue model

With the aid of a 3D printer, researchers at Uppsala University have succeeded in creating a model that resembles human nerve tissue. The model, which can be cultured from the patient's own cells, makes it possible to test new drug treatments in a lab environment.

Motor neurons are nerve cells that control our muscles by sending signals from the brain and spinal cord out to the body. In diseases such as Amyotrophic Lateral Sclerosis (ALS), these cells are destroyed, leading to muscle weakness and paralysis. On average, expected survival after diagnosis is around four years, as the patient's ability to move and breathe gradually deteriorate. There is no cure yet, but some drugs can slow the progression of the disease.

In a new study published in the International Journal of Bioprinting, researchers have shown that it is now possible to use 3D printers to make models, called organoids, that resemble human nerve tissue. These motor neuron organoids can be used in research or to test new drugs for precision medicine, for example.

Motor neurons sit in the middle of the spinal cord, which is why it isn't possible to test treatments directly on a patient who is suffering from a neurodegenerative disease such as ALS. Our method makes it possible to construct motor neuron organoids directly from the patient's skin cells from which we can build spinal cord organoids that can then be used to test new treatments."

Elena Kozlova, lead author of the study

Model produced with 3D printer

In the current study, the researchers used human stem cells generated from skin and programmed to become motor neuron progenitors, a type of immature nerve cell that can later develop into mature motor neurons. The cells were mixed with a soft gelatine and then printed layer by layer with a 3D printer, building up the tissue and its structure. This three-dimensional distribution of the cells in the bioink material improved cell survival and growth of the nerve fibres.

In previous experiments, the neurites only grew on the surface, but the researchers have now managed to get them to grow inside the bioscaffold as well. The solution to this problem was to use a softer 3D printing material (bioink) that retains its shape while still allowing outgrowth of the neurites in the material. To help the cells mature and develop, the researchers used small particles with a porous structure - mesoporous silica particles - that were infused with growth factors and mixed into the bioink material.

Protocol for producing nerve tissue developed

In the study, the researchers present a step-by-step protocol for how to produce more advanced and standardized models of nerve tissue in 3D.

"It's important for research and drug testing to be able to print a large number of organoids in a reproducible way. Our method also makes it possible to include other types of nerve cells including glial cells, which can pave the way for more complete models of the spinal cord," says Elena Kozlova.

This project is part of an international collaboration supported by the Swedish Research Council (Dnr 2019 02240) within the EU Joint Program on Neurodegenerative Diseases (JPND), and by the Swedish National Space Agency (Dnr 2021 0005, Dnr 2024 00211).