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

• Published in: Glia Vol. 69; no. 8; pp. 1916 - 1931
• Main Authors: Baudouin, Lucas, Adès, Noémie, Kanté, Kadia, Czarnecki, Antonny, Bachelin, Corinne, Baskaran, Asha, Langui, Dominique, Millécamps, Aymeric, Gurchenkov, Basile, Velut, Yoan, Duarte, Kévin, Barnier, Jean‐Vianney, Nait Oumesmar, Brahim, Bouslama‐Oueghlani, Lamia
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.08.2021; Wiley Subscription Services, Inc; Wiley
• Subjects: Cell culture; Cell Differentiation - physiology; Cell interactions; cerebellar organotypic cultures; Cerebellum; Coculture Techniques; Differentiation; Electron microscopy; Glial stem cells; Life Sciences; Mental disorders; Microscopy; Molecular modelling; Multiple sclerosis; Myelin; Myelin Sheath - physiology; Myelination; Oligodendrocyte Precursor Cells; Oligodendrocytes; Oligodendroglia - physiology; OPCs; Sheaths; myelination; oligodendrocytes; OPCs; cerebellar organotypic cultures
• ISSN: 0894-1491; 1098-1136
• DOI: 10.1002/glia.24001

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. MAIN POINTS Oligodendrocyte precursor cells transplanted on cerebellar slices, depleted of their endogenous oligodendrocytes, differentiate and form myelin. Exogenous myelin is compact and has the same thickness as the endogenous. Exogenous myelination adopts the same pattern as the endogenous.