The remyelinating potential and in vitro differentiation of MOG-expressing oligodendrocyte precursors isolated from the adult rat CNS.

There is a long-standing controversy as to whether oligodendrocytes may be capable of cell division and thus contribute to remyelination. We recently published evidence that a subpopulation of myelin oligodendrocyte glycoprotein (MOG)-expressing cells in the adult rat spinal cord co-expressed molecules previously considered to be restricted to oligodendrocyte progenitors [G. Li et al.

The presence of astrocytes in areas of demyelination influences remyelination following transplantation of oligodendrocyte progenitors.

To date, most experiments examining the myelination potential of transplanted cells have been undertaken into either the immature nervous system or into acutely demyelinating lesions. Since these are situations where myelination or remyelination are occurring, such studies provide little information on the likely outcome of introducing myelinogenic cells into area of chronic demyelination. In an attempt to gain a greater understanding of the interaction between astrocytes and oligodendrocyte progenitors in areas of demyelination, we undertook transplantation experiments in which an identical preparation of oligodendrocyte progenitors (OPCs) was (1) transplanted directly into astrocyte-free areas of acute demyelination (3 days after induction), (2) transplanted cranial to similar areas of demyelination (20 days after induction) or (3) transplanted cranial to areas of demyelination (20 days after induction) that had been injected with astrocytes at 3 days to confront OPCs with demyelinated axons in an astrocytic environment.

Decline in rate of colonization of oligodendrocyte progenitor cell (OPC)-depleted tissue by adult OPCs with age.

Rates of remyelination decline with age and this has been attributed to slower recruitment of oligodendrocyte progenitor cells (OPCs) into areas of demyelination and slower differentiation of OPCs into remyelinating oligodendrocytes. When considering causes for reduced recruitment rates, intrinsic causes (alterations in biological properties of OPCs) need to be separated from extrinsic causes (age-related differences in the lesion environment). Using 40 Gy of X-irradiation to deplete tissue of its endogenous OPC-population, we examined the effects of age on the rate at which adult rat OPCs colonize OPC-depleted tissue.

Oligodendrocyte progenitor cells in the adult rat CNS express myelin oligodendrocyte glycoprotein (MOG).

While the effects of high dose X-irradiation on mitotically active progenitor cells and remyelination are well-documented, its effects on myelinating oligodendrocytes are less clear, due in part to divergent views on their mitotic capacity. To examine the effect of X-irradiation on oligodendrocytes, the spinal cord of rats was exposed to 40 Gy of X-irradiation and the number of oligodendrocytes and oligodendrocyte progenitors in the dorsal funiculi at T12 and L1 was determined by in situ hybridization using cRNA-probes for platelet derived growth factor alpha receptor (PDGFRalpha) (to identify oligodendrocyte progenitors), exon 3b of proteolipid protein (PLP) (to identify mature oligodendrocytes) and myelin oligodendrocyte glycoprotein (MOG). X-irradiation resulted in no change in the number of PLP positive cells and no loss of myelin internodes, but caused an almost complete loss of PDGFRalpha-expressing cells, and a reduction in the number of MOG positive cells to a number similar to that found using the PLP exon 3b probe.

Modelling large areas of demyelination in the rat reveals the potential and possible limitations of transplanted glial cells for remyelination in the CNS.

Transplantation of myelin-forming glial cells may provide a means of achieving remyelination in situations in which endogenous remyelination fails. For this type of cell therapy to be successful, cells will have to migrate long distances in normal tissue and within areas of demyelination. In this study, 40 Gy of X-irradiation was used to deplete tissue of endogenous oligodendrocyte progenitors (OPCs).