For many years we have thought that after demyelination the remyelination is based from oligodendrocyte precursor cells entering the demyelinating region, based on animal models. However, a bombshell was dropped when people tried to date the age of myelinating cells in MS and they suggested that they come from surviving oligodendrocytes. In this study they looked at Zebra fish
These animals are transparent and you can make them express glo-in the dark myelin so you can see myelination, demyelination and remyelination. The find new myelination coming from precursor cells and that surviving oligodendrocytes have a limited capacity to form new myelin sheaths in vivo. This suggests that therapeutic strategies to promote remyelination through the generation of new oligodendrocytes might be the most promising approach for demyelinating disorders, such as MS.
It would seem unlikely that a basic bit of biology that it has maintained itself from fish to lower mammals like mice and cats would somehow change in humans, but I wish the OPCers would try and repeat the human experiments and show they are not the norm rather than trying to rubbish the human work, e.g. by infering the pathologists had it wrong and the lesions being looked at weren’t remyelinating.
Neely SA, Williamson JM, Klingseisen A, Zoupi L, Early JJ, Williams A, Lyons DA. New oligodendrocytes exhibit more abundant and accurate myelin regeneration than those that survive demyelination. Nat Neurosci. 2022. doi: 10.1038/s41593-021-01009-x.
Oligodendrocytes that survive demyelination can remyelinate, including in multiple sclerosis (MS), but how they do so is unclear. In this study, using zebrafish, we found that surviving oligodendrocytes make few new sheaths and frequently mistarget new myelin to neuronal cell bodies, a pathology we also found in MS. In contrast, oligodendrocytes generated after demyelination make abundant and correctly targeted sheaths, indicating that they likely also have a better regenerative potential in MS.