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Organotypic spinal cord cultures: An in vitro 3D model to preliminary screen treatments for spinal muscular atrophy

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Marina Boido
marina.boido@unito.it
https://orcid.org/0000-0003-1211-1552
Neuroscience Institute Cavalieri Ottolenghi, Department of Neuroscience "Rita Levi Montalcini", University of Turin, Italy.
Elena De Amicis
Neuroscience Institute Cavalieri Ottolenghi, Department of Neuroscience "Rita Levi Montalcini", University of Turin, Italy.
Katia Mareschi
Department of Public Health and Paediatrics, University of Turin; Stem Cell Transplantation and Cellular Therapy Laboratory, Paediatric Onco-Haematology Division, Regina Margherita Children’s Hospital, City of Health and Science of Turin, Italy.
Franca Fagioli
Department of Public Health and Paediatrics, University of Turin; Stem Cell Transplantation and Cellular Therapy Laboratory, Paediatric Onco-Haematology Division, Regina Margherita Children’s Hospital, City of Health and Science of Turin, Italy.
Alessandro Vercelli
Neuroscience Institute Cavalieri Ottolenghi, Department of Neuroscience "Rita Levi Montalcini", University of Turin, Italy.

Spinal muscular atrophy (SMA) is a severe neuromuscular disease affecting children, due to mutation/deletion of survival motor neuron 1 (SMN1) gene. The lack of functional protein SMN determines motor neuron (MN) degeneration and skeletal muscle atrophy, leading to premature death due to respiratory failure. Nowadays, the Food and Drug Administration approved the administration of three drugs, aiming at increasing the SMN production: although assuring noteworthy results, all these therapies show some non-negligible limitations, making essential the identification of alternative/synergistic therapeutic strategies. To offer a valuable in vitro experimental model for easily performing preliminary screenings of alternative promising treatments, we optimized an organotypic spinal cord culture (derived from murine spinal cord slices), which well recapitulates the pathogenetic features of SMA. Then, to validate the model, we tested the effects of human Mesenchymal Stem Cells (hMSCs) or murine C2C12 cells (a mouse skeletal myoblast cell line) conditioned media: 1/3 of conditioned medium (obtained from either hMSCs or C2C12 cells) was added to the conventional medium of the organotypic culture and maintained for 7 days. Then the slices were fixed and immunoreacted to evaluate the MN survival. In particular we observed that the C2C12 and hMSCs conditioned media positively influenced the MN soma size and the axonal length respectively, without modulating the glial activation. These data suggest that trophic factors released by MSCs or muscular cells can exert beneficial effects, by acting on different targets, and confirm the reliability of the model. Overall, we propose the organotypic spinal cord culture as an excellent tool to preliminarily screen molecules and drugs before moving to in vivo models, in this way partly reducing the use of animals and the costs.

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How to Cite

Boido, M., De Amicis, E., Mareschi, K., Fagioli, F., & Vercelli, A. (2021). Organotypic spinal cord cultures: An <em>in vitro</em> 3D model to preliminary screen treatments for spinal muscular atrophy. European Journal of Histochemistry, 65(s1). https://doi.org/10.4081/ejh.2021.3294
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