A research team at Uppsala University has developed an innovative method to produce three-dimensional motor nerve cell organoids using a patient’s own skin cells. This advancement aims to facilitate realistic laboratory testing of new therapeutic compounds targeting neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). The findings were published in the International Journal of Bioprinting.

ALS progressively damages motor neurons in the spinal cord, leading to muscle weakness and eventual respiratory failure. Direct testing on the spinal cord of affected individuals is not feasible due to medical limitations. To address this, the team led by Elena Kozlova created an in-vitro model. Skin-derived cells were reprogrammed into induced pluripotent stem cells, differentiated into motor neuron precursors, and embedded in a gelatinous hydrogel. These were then assembled layer by layer using 3D printing technology.

The resulting organoids replicate motor neuron structures and can be derived directly from individual patients, allowing for personalized spinal cord models. These can then be used to evaluate potential treatments in conditions that closely mimic the human nervous system.

A key factor in the success of this method was selecting a soft bio-ink that supports both the structural integrity of the construct and the growth of neurites. Porous silica particles containing embedded growth factors were also included to enhance neuronal maturation.

Unlike earlier methods where neurite growth was confined to the surface, this approach enabled deep cell architecture development within the matrix. This not only improves structural similarity to the actual spinal cord but also increases the relevance of the model for drug testing.

The method also allows for the incorporation of additional nerve cell types, such as glial cells, making it possible to create more comprehensive spinal cord models. Furthermore, the team has established a reproducible protocol for standardized organoid production, making the technology scalable and suitable for preclinical and precision medicine research in neurodegeneration.

By Impact Lab