Picture: Tobias Sterner/Bildbyrån
A research team at Uppsala University has developed a method for producing motor nerve cells in the form of three-dimensional organoids from a patient’s own skin cells. The aim is to test new active substances against neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) under realistic conditions in the laboratory. The results were published in the International Journal of Bioprinting.
ALS gradually destroys motor neurons in the spinal cord, leading to muscle weakness and ultimately to respiratory paralysis. Clinical tests directly on the spinal cord of people with the disease are hardly feasible from a medical point of view. The method developed by Elena Kozlova and her team therefore relies on an in-vitro model: induced pluripotent stem cells obtained from skin cells are differentiated into motor neuron precursors, embedded in a gelatinous hydrogel and then built up in a layer-by-layer structure using 3D printing.
“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,” says Elena Kozlova, lead author of the study.Model produced with 3D printer
The selection of a particularly soft bio-ink was crucial for cell maturation and the growth of the neurites inside the biocarrier, which both maintains dimensional stability and allows the cell processes to grow in. In addition, porous silica particles with embedded growth factors were used to further support neuronal maturation.
In contrast to previous approaches, in which neurites only developed on the surface, it was now possible to build up the cell architecture deep into the matrix. This not only improves the structural similarity to the human spinal cord, but also the applicability for pharmacological tests.
“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.
The team has also created a reproducible protocol for the standardized production of such organoids. This makes the method scalable and usable for preclinical research – especially for precision medicine approaches in neurodegeneration.