Endogenous Progenitors Remyelinate Demyelinated Axons in the Adult CNS

Abstract

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.

Cell Therapy for Multiple Sclerosis

“…Human oligodendrocyte progenitors showed similar capacity to disseminate white matter throughout the brain in these models [131]. However, in the lesioned adult CNS, there is limited migration of endogenous remyelinating cells resulting in local remyelination that may be insufficient for widespread lesions [50,256].…”

“…Differentiated postmitotic oligodendrocytes are unable to rebuild myelin sheaths [45][46][47] and remyelination is dependent on cycling cells [47,48]. The notion that OPCs are the main remyelinating cells of the adult CNS emerged from studies showing remyelination after focal demyelination by resident progenitor cells [49,50]. Tissue OPCs expressing NG2 and platelet-derived growth factor receptor-α on their cell surface are mobilized in response to demyelination [49,[51][52][53].…”

“…In addition cell migration seems to be another limiting factor in myelin regeneration. Progenitor cells that reside at the margins of experimental lesions migrate into the lesion core and remyelinate it, but long distance migration does not occur in the brain parenchyma [50,81]. The limited recruitment of adult CNS OPCs into demyelinated lesions may be also related to their apparent dormant state.…”

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).…”

Electrical signalling properties of oligodendrocyte precursor cells

“…Damage to oligodendrocyte precursors, leading to reduced myelination, contributes to mental and physical impairment in periventricular leukomalacia (pre-or perinatal white matter injury leading to cerebral palsy; Volpe, 2001). Adult OPCs may form new myelinating oligodendrocytes in multiple sclerosis, and in brain or spinal cord injury (Levine, 1994;Gensert and Goldman, 1997;Keirstead et al, 1998;McTigue et al, 2001;Levine et al, 2001;Horner et al, 2002), and OPC transplants could serve as a basis for therapeutic remyelination (Windrem et al, 2008;Moreno-Manzano et al, 2009). This article will focus on the electrical signalling properties of OPCs which, as we will describe below, may play a crucial role in their development and their myelination of axons.…”