Long-term Oligodendrocyte Cultures: an In Vitro Model to Study their Biology

  Because the protocol we have developed uses white matter as the source of OLGs and because prior to plating the cells are exposed to antimitotic agents to kill all proliferating cells, including OLG progenitors, the surviving cells are all post-myelination. This culture, in itself, becomes an in vitro model for addressing the question: what happens to OLGs when they are separated from the myelin sheath? A question that is relevant to MS. It is the general belief that mature (post-myelination) OLGs seen in the vicinity of MS plaques are unable to remyelinate ^[1]. Our findings revealed the opposite; they demonstrate that such OLGs can be reprogrammed to re-enact the myelinogenic metabolism provided they are given the necessary signal ^{[2, 3]}. In vitro this signal is generated by their adhesion to a specific substratum ^[4-6]. Hence, there are two possible explanations for the inactivity of mature OLGs in MS: 1) the signal is missing; or 2) OLGs are sick. Interestingly, while MS is still considered an autoimmune disease, evidence is shifting to the notion that this may be secondary to an initial affliction of OLGs.

  We characterized these cultures biochemically, morphologically, structurally, immunologically, and electrophysiologically. Overall the data revealed these cultured OLGs to re-enact developmental events in vivo ^[7-10]. Salient findings are described in subsequent sections.