Regeneration and repair in multiple sclerosis: The view of experimental pathology

In order to devise a strategy to enhance remyelination in multiple sclerosis (MS) it is necessary to understand the cause of remyelination failure in MS. A case is made that areas of chronic demyelination arise because of concurrent loss of oligodendrocyte progenitor cells (OPCs) and oligodendrocytes and that because of the slow rate of repopulation that occurs in old individuals the recruited OPCs are not exposed to the acute inflammatory environment required to generate remyelinating oligodendrocytes. Based on this analysis the case is made that only areas of acute demyelination will be amenable to transplant-mediated remyelination. An analysis of the many cells that could be used to provide a source of remyelinating cells would indicate that structural repair of the CNS in MS would likely only be possible if neural precursors were used and the most promising route for their introduction would appear to be by intraventricular injection. Both neural precursors and mesenchymal stromal cells can be immunomodulatory and neuroprotective following intravenous injection; however, only neural precursors are likely to be able to contribute to structural repair of the damaged nervous system.