What roles do growth factors play in CNS remyelination?

Identifying a source of cells with the capacity to generate oligodendrocytes in the adult CNS would help in the development of strategies to promote remyelination. In the present study, we examined the ability of the precursor cells of the adult mouse subventricular zone (SVZ) to differentiate into remyelinating oligodendrocytes. After lysolecithin-induced demyelination of the corpus callosum, progenitors of the rostral SVZ (SVZa) and the rostral migratory pathway (RMS), expressing the embryonic polysialylated form of the neural cell adhesion molecule (PSA-NCAM), increased progressively with a maximal expansion occurring after 2 weeks. This observation correlated with an increase in the proliferation activity of the neural progenitors located in the SVZa and RMS. Moreover, polysialic acid (PSA)-NCAM-immunoreactive cells arizing from the SVZa were detected in the lesioned corpus callosum and within the lesion. Tracing of the constitutively cycling cells of the adult SVZ and RMS with 3H-thymidine labelling showed their migration toward the lesion and their differentiation into oligodendrocytes and astrocytes but not neurons. These data indicate that, in addition to the resident population of quiescent oligodendrocyte progenitors of the adult CNS, neural precursors from the adult SVZ constitute a source of oligodendrocytes for myelin repair.

The oligodendrocyte (OL) is increasingly providing a model system for probing central issues of cell biology. During development, OL progenitors undergo controlled migration, proliferation and differentiation, secrete and respond to a number of growth factors, and dramatically change their cellular architecture, culminating in the formation of the myelin sheath. This review examines some facets of the OL that make it an especially attractive tool for studying many basic questions in cell biology.

Remyelination occurs in demyelinated CNS regions in diseases such as multiple sclerosis. Identification of the cell type(s) responsible for this remyelination, however, has been elusive. Here, we examine one potential source of remyelinating oligodendrocytes-immature, cycling cells endogenous to adult white matter-and demonstrate that this population responds to demyelination by differentiating into myelinating oligodendrocytes. Dividing cells in subcortical white matter of adult rats were labeled by stereotactic injection of a replication-deficient lacZ-encoding retrovirus (BAG). Following a focal demyelination induced with lysolecithin, many of the BAG-labeled cells differentiated into myelinating oligodendrocytes engaging in repair of the lesion. Identification of endogenous cells capable of remyelination provides a target for the study of CNS repair processes in demyelinating diseases.