Pre-oligodendrocytes from adult human CNS

Abstract

CNS remyelination and functional recovery often occur after experimental demyelination in adult rodents. This has been attributed to the ability of mature oligodendrocytes and/or their precursor cells to divide and regenerate in response to signals in demyelinating lesions. To determine whether oligodendrocyte precursor cells exist in the adult human CNS, we have cultured white matter from patients undergoing partial temporal lobe resection for intractable epilepsy. These cultures contained a population of process-bearing cells that expressed antigens recognized by the O4 monoclonal antibody, but these cells did not express galactocerebroside (a marker for oligodendrocytes), glial fibrillary acidic protein (a marker for astrocytes), or vimentin. Selective elimination of O4-positive (O4+) cells by complement-mediated lysis resulted in inhibition of oligodendrocyte development in vitro. Since O4+ cells have an antigenic phenotype reminiscent of the rat adult oligodendrocyte-type 2 astrocyte progenitor and appear to develop into oligodendrocytes rather than type 2 astrocytes with time in culture, we call them "pre-oligodendrocytes." Neither pre-oligodendrocytes nor oligodendrocytes incorporated 3H-thymidine in response to rat astrocyte-conditioned medium, platelet-derived growth factor, insulin-like growth factor (IGF-1), or basic fibroblast growth factor (bFGF). However, IGF-1 increased the relative abundance of oligodendrocytes to pre-oligodendrocytes, while bFGF had the opposite effect. Cells with the antigenic phenotype of pre-oligodendrocytes were also identified in tissue prints of adult human white matter. We propose that, in human demyelinating diseases such as multiple sclerosis, pre-oligodendrocytes may divide and/or migrate in response to signals present in demyelinated lesions and thus facilitate remyelination.

Distinctive Properties of Human Adult Brain-Derived Myelin Progenitor Cells

“…Most available rodent data have been generated using OLGs that have been matured in vitro. 28,30 -32 Previously we 33 reported, consistent with results of Armstrong and colleagues 34 that immediately on isolation a proportion of cells within the mature OLG fraction express early myelin lineage markers (A007) and not mature markers (MBP). Armstrong and colleagues 34 speculated this may represent dedifferentiation of the cells during the isolation procedure.…”

Late Oligodendrocyte Progenitors Coincide with the Developmental Window of Vulnerability for Human Perinatal White Matter Injury

“…In adult human brain, NG2ϩ progenitors appear to be oligodendroglial in origin and as abundant as mature OLs (Chang et al, 2000). The relationship of these progenitors to pre-OLs in fetal or adult (Armstrong et al, 1992;Wolswijk, 1998) human brain is presently unclear. Because adult NG2-positive progenitors would appear to be more abundant than we observed in developing human brain, it is possible that adult human progenitors may subserve more diverse functions than during development.…”

miR-23regulation of lamin B1 is crucial for oligodendrocyte development and myelination

“…The mouse fibroblasts were isolated from adult LMNB1-overexpressing transgenic mice (unpublished data) following standard procedures (Xu et al, 2007). Primary glial cultures were performed using standard methods (McCarthy and de Vellis, 1980;Armstrong et al, 1992;Dugas et al, 2006). Plasmid or single-stranded RNA transfection was performed by using FuGene HD (Roche) or nucleofector electroporation with the Amaxa system (Amaxa Biosystems).…”