Neural stem cells as a potential source of oligodendrocytes for myelin repair

Neural stem cells (NSCs) are considered to have widespread therapeutic possibilities on account of their ability to provide large numbers of cells whilst retaining multi-potentiality. Application to human demyelinating diseases requires improved understanding of the signalling requirements underlying the generation of oligodendrocytes from NSCs. During development, spinal cord oligodendrocyte precursors (OPCs) originate from the ventral, but not dorsal neuroepithelium due to the regulatory effects of the morphogen Sonic hedgehog (Shh). The developing human spinal cord shows comparable ventral-dorsal gradient of oligodendrocyte differentiation potential to the embryonic rodent spinal cord. In contrast expanded human neural precursors derived from both isolated ventral or dorsal cultures show a reduced capacity to generate oligodendrocytes, whereas comparable rodent cultures demonstrate a marked increase in oligodendrocyte formation by a hedgehog independent pathway. Inter-species difference in the capacity of neural precursors to generate oligodendrocytes emphasises the need for greater study of human derived stem cell populations.