Journal
GLIA
Volume 69, Issue 8, Pages 1916-1931Publisher
WILEY
DOI: 10.1002/glia.24001
Keywords
cerebellar organotypic cultures; myelination; oligodendrocytes; OPCs
Categories
Funding
- Fondation Marie-Ange Bouvet-Labruyere
- Fondation pour l'Aide a la Recherche sur la Sclerose en Plaques [R18103DD, R19233DD]
- Program Investissements d'avenir [ANR-10-IAIHU-06]
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Researchers have developed a reliable ex vivo model of myelination by seeding OPCs on cerebellar slices deprived of their endogenous oligodendrocytes. This model is an effective tool for studying the cellular and molecular mechanisms of OPC differentiation and myelination, and can aid in the development and validation of new therapies for myelin-related disorders such as multiple sclerosis and psychiatric diseases.
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.
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