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

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 respirator...

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Autores principales:	Marina Boido, Elena De Amicis, Katia Mareschi, Franca Fagioli, Alessandro Vercelli
Formato:	article
Lenguaje:	EN
Publicado:	PAGEPress Publications 2021
Materias:	3D cell culture motor neuron disease drug screening Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/bbba8f6e51404cb6b0df6e4954d4f06e
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spelling	oai:doaj.org-article:bbba8f6e51404cb6b0df6e4954d4f06e2021-11-05T07:36:06ZOrganotypic spinal cord cultures: An <em>in vitro</em> 3D model to preliminary screen treatments for spinal muscular atrophy10.4081/ejh.2021.32941121-760X2038-8306https://doaj.org/article/bbba8f6e51404cb6b0df6e4954d4f06e2021-11-01T00:00:00Zhttps://www.ejh.it/index.php/ejh/article/view/3294https://doaj.org/toc/1121-760Xhttps://doaj.org/toc/2038-8306 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. Marina BoidoElena De AmicisKatia MareschiFranca FagioliAlessandro VercelliPAGEPress Publicationsarticle3D cell culturemotor neuron diseasedrug screeningBiology (General)QH301-705.5ENEuropean Journal of Histochemistry , Vol 65, Iss s1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	3D cell culture motor neuron disease drug screening Biology (General) QH301-705.5
spellingShingle	3D cell culture motor neuron disease drug screening Biology (General) QH301-705.5 Marina Boido Elena De Amicis Katia Mareschi Franca Fagioli Alessandro Vercelli Organotypic spinal cord cultures: An <em>in vitro</em> 3D model to preliminary screen treatments for spinal muscular atrophy
description	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.
format	article
author	Marina Boido Elena De Amicis Katia Mareschi Franca Fagioli Alessandro Vercelli
author_facet	Marina Boido Elena De Amicis Katia Mareschi Franca Fagioli Alessandro Vercelli
author_sort	Marina Boido
title	Organotypic spinal cord cultures: An <em>in vitro</em> 3D model to preliminary screen treatments for spinal muscular atrophy
title_short	Organotypic spinal cord cultures: An <em>in vitro</em> 3D model to preliminary screen treatments for spinal muscular atrophy
title_full	Organotypic spinal cord cultures: An <em>in vitro</em> 3D model to preliminary screen treatments for spinal muscular atrophy
title_fullStr	Organotypic spinal cord cultures: An <em>in vitro</em> 3D model to preliminary screen treatments for spinal muscular atrophy
title_full_unstemmed	Organotypic spinal cord cultures: An <em>in vitro</em> 3D model to preliminary screen treatments for spinal muscular atrophy
title_sort	organotypic spinal cord cultures: an <em>in vitro</em> 3d model to preliminary screen treatments for spinal muscular atrophy
publisher	PAGEPress Publications
publishDate	2021
url	https://doaj.org/article/bbba8f6e51404cb6b0df6e4954d4f06e
work_keys_str_mv	AT marinaboido organotypicspinalcordculturesaneminvitroem3dmodeltopreliminaryscreentreatmentsforspinalmuscularatrophy AT elenadeamicis organotypicspinalcordculturesaneminvitroem3dmodeltopreliminaryscreentreatmentsforspinalmuscularatrophy AT katiamareschi organotypicspinalcordculturesaneminvitroem3dmodeltopreliminaryscreentreatmentsforspinalmuscularatrophy AT francafagioli organotypicspinalcordculturesaneminvitroem3dmodeltopreliminaryscreentreatmentsforspinalmuscularatrophy AT alessandrovercelli organotypicspinalcordculturesaneminvitroem3dmodeltopreliminaryscreentreatmentsforspinalmuscularatrophy
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Organotypic spinal cord cultures: An <em>in vitro</em> 3D model to preliminary screen treatments for spinal muscular atrophy

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