Identification of A2B5-positive putative oligodendrocyte progenitor cells and A2B5-positive astrocytes in adult human white matter

Abstract

Spontaneous remyelination of previously demyelinated axons is found in a substantial minority of acute and chronic lesions in multiple sclerosis. In the rodent, central remyelination restores saltatory conduction and helps restore limb function, and it seems likely that endogenous myelin repair contributes to neurological recovery in multiple sclerosis. However, the identity of the remyelinating cell remains enigmatic. Fully differentiated oligodendrocytes have very limited capacity for recapitulating their developmental activities and re-engaging myelination pathways. Proliferative oligodendrocyte progenitors--often known as O-2A cells because of their ability to differentiate in vitro into either oligodendrocytes or ("type 2") astrocytes--are, in contrast, extremely efficient at myelin repair either spontaneously, or after transplantation into the de- or dysmyelinated CNS. Oligodendrocyte progenitors are present in both developing and adult rodent CNS. We have previously demonstrated that proliferative oligodendrocyte progenitors are present in cultures prepared from the adult human CNS. Here, using fresh tissue print preparations, we report that cells with processes and the A2B5-positive immunophenotype of proliferative oligodendrocyte progenitors are present in situ in adult human white matter. This technique also reveals the occurrence of A2B5-positive astrocytes, a cell also not previously identified in the normal adult human CNS. In the light of the rodent data showing the importance of oligodendrocyte progenitors in myelin repair, our findings suggesting the presence of progenitors in the adult human brain may have significant implications for spontaneous remyelination in multiple sclerosis and other demyelinating conditions.