Progenitor cells of the adult mouse subventricular zone proliferate, migrate and differentiate into oligodendrocytes after demyelination

Abstract

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.

Cell Therapy for Multiple Sclerosis

“…Recent studies provided the definitive proof that these cells are indeed the main remyelinating cell in the CNS following a demyelinating injury [54,55]. In addition, neural precursor cells (NPCs) of the adult SVZ expressing the embryonic polysialylated form of the neural cell adhesion molecule (PSA-NCAM) react to inflammation and demyelination with proliferation, and migration into the tissue and glial differentiation, generating both astrocytes and remyelinating oligodendrocytes [56][57][58][59].…”

“…The inflammatory process in the CNS of EAE animals was found to be a powerful stimulus stimulating subventricular PSA-NCAM+ cells [56,57] and attracting targeted migration of transplanted neural and oligodendroglial precursor cells [94,95,257]. Following ICV transplantation of neurospheres, cells migrated into inflamed periventricular white matter tracts, and differentiated mainly into glial progeny.…”

Expression of the transcription factor Olig2 in proliferating cells in the adult zebrafish telencephalon

“…In the adult mammalian brain, it is known that slowly cycling oligodendrocyte progenitor cells (OPCs), which express the basic Helix-Loop-Helix (bHLH) transcription factor Olig2 and the HMG-box transcription factor Sox10, are distributed throughout the brain producing oligodendrocytes that can participate in myelin repair (Wolswijk and Noble, 1989;Gensert and Goldman, 1997;Nait-Oumesmar et al, 1999;Chari and Blakemore, 2002;Polito and Reynolds, 2005;Aguirre et al, 2007). OPCs are the major dividing cell population in the adult brain of mammals (Dawson et al, 2003;Geha et al, 2009).…”

The effect of triiodothyronine on maturation and differentiation of oligodendrocyte progenitor cells during remyelination following induced demyelination in male albino rat

“…It generates the most abundant number of stem cells in the adult brain that are capable of migrating to a long distance (Maki et al, 2013). These endogenous progenitors react to demyelinating lesions and generate remyelinating oligodendrocytes (Nait-Oumesmar et al, 1999).…”