PHENOTYPIC AND CELL-CYCLE PROPERTIES OF HUMAN OLIGODENDROCYTES IN-VITRO

The remyelination, albeit limited, which occurs at the lesion sites in the central nervous in multiple sclerosis has been attributed to both myelin production by previously myelinating cells and to precursor cells which mature into myelin-producing cells, Oligodendrocyte (OL) number may be increased at the periphery of the lesions. In this study, we assessed the state of maturation and cell cycle-dependent properties of OLs derived from surgically resected adult human cerebral cortex specimens. In 6-day-old OL cultures, a small proportion of cells (14.1+/-3.5%: range 4-24%) expressed an immature phenotype, defined as A007(+):myelin basic protein (MBP)-negative. Using lack of statin expression as an index of cells exiting the G0 phase of the cell cycle, we observed that 4.6+/-1.6% of A007(+) cells, but only rare MBP(+) cells (0.4+/-1.8%) were non-reactive with the anti-statin antibody, S44. The proportion of non-statin-reactive cells was not affected by treatment with basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) or insulin-like growth factor (IGF). The oligodendrocytes did not incorporate BrdU during a 48-h pulse and did not immunoreact with Ki-67 antibody. In 4-week-old cultures, we found that all A007(+) cells were also MBP(+) and that 99.5+/-0.7% were statin-positive. Exposing 4-week-old OLs to conditions of serum deprivation or to 1,000 units/ml of recombinant human TNF-beta for 4 days induced nuclear fragmentation in a high proportion (> 70%) of cells, as measured by a TUNEL technique; in these cultures, a similarly high proportion of cells were non-immunoreactive with anti-statin antibody. Our results suggest that a small number of phenotypic 'pre-oligodendrocytes' can be derived from the adult human CNS and that a proportion of these cells have exited the G0 phase of the cell cycle. Attempt at cell cycling, however, could reflect abortive mitosis and activation of programmed cell death.