The origin of remyelinating cells in the adult central nervous system: the role of the mature oligodendrocyte

Abstract

The sequence of events by which new oligodendrocytes are generated in the adult mammalian central nervous system has not been clearly defined. Here we review old evidence that remyelinating cells can arise from the division of mature oligodendrocytes. In addition, we report the results of a tissue culture study comparing oligodendrocytes and immature progenitors with regard to their capacity for proliferation, for the generation of new oligodendrocytes and for myelination. Monoclonal antibodies 04 and 01 were used to distinguish oligodendrocytes (04+01+) from progenitors (04+01-). Dissociated cell suspensions from adult rat spinal cord were separated by flow cytometry into 01+ and 01- cell fractions, at greater than 93% purity. The 01+ fraction contained approximately 0.7% 04+01- cells while the 01- fraction contained approximately 4.4% 04+01- cells. Cells from these fractions were plated onto cultures of purified dissociated dorsal root ganglion neurons. The cultures that received 01+ cells developed numerous expanding colonies of cells expressing both 01 and 04, or 04 only, by 8 days and were essentially covered by oligodendrocytes by 16 days. In marked contrast, oligodendrocyte colonies were rare in cultures receiving 01- cells. By 24 days, myelination was extensive in cultures receiving 01+ cells; in contrast, only a few myelin segments were observed in cultures receiving the 01- fraction. Thus, oligodendrocytes (01+ cells) appear more capable than progenitors (04+01-) of generating new myelinating oligodendrocytes in this culture system.