Medical & Dental

3D Printed Motor Neuron Organoids by Uppsala Researchers Could Accelerate ALS Drug Development

Researchers at Uppsala University in Sweden have developed 3D printed models from patient-derived cells to simulate motor neurons in the lab. These structures, known as motor neuron organoids, are expected to support research into neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS) and help explore treatment strategies without the need for invasive procedures.

Understanding ALS and Bioprinting Breakthrough

Motor neurons are nerve cells that transmit signals from the brain and spinal cord to muscles, enabling movement. In ALS, these neurons progressively deteriorate, leading to muscle weakness, paralysis, and, eventually, the inability to breathe. While the disease currently has no cure, some treatments can help slow its progression. On average, patients live about four years after diagnosis.

In a recent study published in the International Journal of Bioprinting, Uppsala researchers showed that 3D printers can now be used to create motor neuron organoids that closely resemble human nerve tissue. These models can be used in precision medicine to test potential therapies tailored to individual patients.

“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,” said Elena Kozlova, lead author of the study.

Elena Kozlova, the main researcher. Photo via Uppsala University.
Elena Kozlova, lead author of the study. Photo via Uppsala University.

Building the Model

To create the organoids, the researchers reprogrammed skin-derived human stem cells into motor neuron progenitors—immature cells capable of developing into fully functioning motor neurons. These cells were then embedded in a soft, gelatin-based material and printed layer by layer using a 3D printer. The process allowed for a more even distribution of cells within the bioink, improving both cell survival and nerve fiber growth.

Previous experiments had limited success, as neurites only grew on the surface of the printed material. By switching to a softer bioink that retained its shape while allowing internal growth, the team achieved better integration. To further support cell maturation and development, the researchers incorporated mesoporous silica particles—tiny, porous structures— infused with growth factors into the bioink material.

In addition to demonstrating the feasibility of the technique, the researchers also shared a step-by-step protocol for creating advanced and reproducible 3D nerve tissue models. “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,” sayid Kozlova.

Motor neurons that have been generated from human stem cells. Photo via Uppsala University.
Motor neurons that have been generated from human stem cells. Photo via Uppsala University.

Advances in 3D Printing for Nerve Repair

In 2018, Scientists in the Tissue Engineering Research Group at the University of Saskatchewan, Canada, have made progress in the treatment of damaged peripheral nerves using 3D printing. Their findings showed that 3D printed tissue scaffolds could be used to repair, or regenerate damaged nerves connecting the spine and the brain to the rest of the body.

Elsewhere, researchers at the Chinese Academy of Sciences and University of Science and Technology of China devised a bioprinting-based method of curing previously untreatable spinal cord injuries.  Using a custom-designed bio-ink, the team successfully 3D bioprinted neural stem cell-loaded tissues capable of transmitting neural signals from the brain, mimicking the communication seen in living organisms. When implanted into paralyzed rats, these scaffolds facilitated the restoration of limb movement, suggesting potential for future human applications.

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Featured image shows motor neurons that have been generated from human stem cells. Photo via Uppsala University.

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