Oligodendrocytes and stem cell transplantation: their potential in the treatment of leukoencephalopathies.

Cell transplantation is being extensively explored as a means of treating many human degenerative diseases. The leukodystrophies are examples of neurological disorders where new therapeutic strategies, either cellular or molecular, will be required to repair the central nervous system (CNS) of affected patients. Much hope is being pinned on the use of human embryonic stem (ES) cells as the exogenous source of neurons and glia to replace dysfunctional or dying cells in the CNS. In the case of leukoencephalopathies, the goal is to generate oligodendrocytes or other myelinating cells such as Schwann cells from ES cells, to myelinate or remyelinate CNS axons on transplantation. Experimental data suggests that mouse ES cells have this capacity, but at present differentiation of oligodendrocytes in sufficient numbers from human ES cells is not possible. It may in fact be more feasible to isolate oligodendrocytes from human neural stem cells derived from the fetal brain, but the source of these is in short supply and, like that of ES cells, is ethically controversial. None the less, it appears certain that either of these two sources will eventually give rise to sufficient numbers of neural stem cells or oligodendrocyte progenitors that have greater capacity for repair than such cells derived from the adult brain. Once the primary technical issues concerning human ES cell differentiation have been overcome, the most likely first clinical target will be Pelizaeus-Merzbacher disease. However, widespread dissemination of cells throughout the CNS may be required for functional improvement; hence diseases such as adrenoleukodystrophy may also be considered as therapeutic targets.