Glia. 2021 Aug;69(8):1916-1931. doi: 10.1002/glia.24001. Epub 2021 Apr 02.

Co-culture of exogenous oligodendrocytes with unmyelinated cerebella: Revisiting ex vivo models and new tools to study myelination.

Glia

Lucas Baudouin, Noémie Adès, Kadia Kanté, Antonny Czarnecki, Corinne Bachelin, Asha Baskaran, Dominique Langui, Aymeric Millécamps, Basile Gurchenkov, Yoan Velut, Kévin Duarte, Jean-Vianney Barnier, Brahim Nait Oumesmar, Lamia Bouslama-Oueghlani

PMID: 33811384 DOI: 10.1002/glia.24001

Abstract

Common in vitro models used to study the mechanisms regulating myelination rely on co-cultures of oligodendrocyte precursor cells (OPCs) and neurons. In such models, myelination occurs in an environment that does not fully reflect cell-cell interactions and environmental cues present in vivo. To avoid these limitations while specifically manipulating oligodendroglial cells, we developed a reliable ex vivo model of myelination by seeding OPCs on cerebellar slices, deprived of their endogenous oligodendrocytes. We showed that exogenous OPCs seeded on unmyelinated cerebella, efficiently differentiate and form compact myelin. Spectral confocal reflectance microscopy and electron microscopy analysis revealed that the density of compacted myelin sheaths highly increases all along the culture. Importantly, we defined the appropriate culture time frame to study OPC differentiation and myelination, using accurate quantification resources we generated. Thus, this model is a powerful tool to study the cellular and molecular mechanisms of OPC differentiation and myelination. Moreover, it is suitable for the development and validation of new therapies for myelin-related disorders such as multiple sclerosis and psychiatric diseases.

© 2021 Wiley Periodicals LLC.

Keywords: OPCs; cerebellar organotypic cultures; myelination; oligodendrocytes

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Grant support

• Fondation Marie-Ange Bouvet-Labruyère
• R18103DD/Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques
• R19233DD/Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques
• Program "Investissements d'avenir" ANR-10-IAIHU-06