3D Spinal Cord Networks: ECM Molecules and Glial Cells Enable Disease Modeling
Dr Natascha Schäfer
Institut für klinische Neurobiologie
Universiätsklinikum Würzburg
Germany
3D Spinal Cord Networks: ECM Molecules and Glial Cells Enable Disease Modeling
Abstract: Some complex neurological diseases, especial their molecular pathomecanisms remain poorly understood, most probably due to the limitations of conventional 2D cell culture models, which fail to mimic a third dimension or even the main characteristics of the tissue. This highlights the need for efficient 3D models to study neurological diseases, particularly as transgenic animal models are cost-intensive, ethically controversial, and often unsuitable for rare diseases. However, creating a 3D spinal cord model for studying neurological diseases presents significant challenges, due to the tissue's complexity of primary cell types and due to its ultra soft character. To address these challenges, a MEW-printed PCL scaffold is used, which serves as a reinforcing structure for the use of an ultrasoft hydrogel resembling the extracellular matrix (ECM)of spinal cord tissue. Of further interest are the interactions between cellular components, like astrocytes and the ECM, especially laminins, as they are essential for motoneuronal survival, network formation, and function. This knowledge was used to establish and validate a 3D spinal cord model to study cell-cell interactions and neuronal maturation and functional in health and disease condition. As disease condition the neurological disorder stiff person syndrome, an autoimmune disorder is used to evaluate the ability to study pathomechanisms in 3D.
After successful validation, the model system is intended to be further developed to investigate other neurodegenerative diseases underlying the spinal cord e.g. spinal muscular atrophy or amyotrophic lateral sclerosis. In addition, the system is adapted to be used in studies involving cortical neurons in the context of Parkinson’s disease. In this case it is of special interest to include interactions of the immune system as those cell types have been left out in the current 3D models.
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