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Cell transplant therapies are currently under active consideration for a number of degenerative diseases. In the immune-mediated demyelinating-neurodegenerative disease multiple sclerosis (MS), only the myelin sheaths of the CNS are lost, while Schwann cell myelin of the PNS remains normal. This, and the finding that Schwann cells can myelinate CNS axons, has focussed interest on Schwann cell transplants to repair myelin in MS. However, the experimental use of these cells for myelin repair in animal models has revealed a number of problems relating to the incompatibility between peripheral glial cells and the CNS glial environment. Here, we have tested whether these difficulties can be avoided by using an earlier stage of the Schwann cell lineage, the Schwann cell precursor (SCP). For direct comparison of these two cell types, we implanted Schwann cells from post-natal rat nerves and SCPs from embryo day 14 (E14) rat nerves into the CNS under various experimental conditions. Examination 1 and 2 months later showed that in the presence of naked CNS axons, both types of cell form myelin that antigenically and ultrastructurally resembles that formed by Schwann cells in peripheral nerves. In terms of every other parameter we studied, however, the cells in these two implants behaved remarkably differently. As expected from previous work, Schwann cell implants survive poorly unless the cells find axons to myelinate, the cells do not migrate significantly from the implantation site, fail to integrate with host oligodendrocytes and astrocytes, and form little myelin when challenged with astrocyte-rich environment in the retina. Following SCP implantation, on the other hand, the cells survive well, migrate through normal CNS tissue, interface smoothly and intimately with host glial cells and myelinate extensively among the astrocytes of the retina. Furthermore, when implanted at a distance from a demyelinated lesion, SCPs but not Schwann cells migrate through normal CNS tissue to reach the lesion and generate new myelin. These features of SCP implants are all likely to be helpful attributes for a myelin repair cell. Since these cells also form Schwann cell myelin that is arguably likely to be resistant to MS pathology, they share some of the main advantages of Schwann cells without suffering from the disadvantages that render Schwann cells less than ideal candidates for transplantation into MS lesions.

Following spinal cord trauma there is controversy as to whether myelin-supporting oligodendrocytes at a distance from areas of spinal cord damage undergo apoptosis. To examine the response of oligodendrocytes to axon degeneration, we counted the number of oligodendrocytes and oligodendrocyte precursors in the dorsal funiculi during the course of Wallerian degeneration. Axons were disrupted at T13 and the number of labelled cells in the dorsal funiculi counted at T12, 4 days and 2, 4, and 8 weeks after injury using riboprobes to exon-3b of the PLP gene whose expression is considered to restricted to myelin-supporting oligodendrocytes, PDGFRalpha which is regarded as a marker of oligodendrocyte precursors, and MOG a marker previously used to identify myelin-supporting oligodendrocytes. We found that the number of PLP-exon-3b labelled cells remained constant during the course of Wallerian degeneration while the number of cells labelled with the riboprobes to PDGFRalpha and MOG increased. Significantly the number of MOG-positive cells was increased at times when the number of PDGFRalpha labelled cells was highest. The number of PDGFRalpha labelled cells decreased with time while the number PLP-exon-3b labelled cells remained constant. It is therefore possible that the apoptotic oligodendrocytes identified in previous studies could represent degenerating oligodendrocyte precursors or their progeny rather than degenerating myelin-supporting oligodendrocytes.

ONE of the outstanding characteristics of multiple sclerosis and other clinical and experimental diseases associated with demyelination, is the tendency to remit. Although there is good evidence that an important cause of functional loss in such conditions is conduction block produced by the selective destruction of the myelin sheath1, the mechanisms underlying remission are unknown2. It has long been recognised that in certain experimental lesions demyelinated central axons can be remyelinated by the normal myelin-forming cell, the oligodendrocyte3. The new sheaths are, however, abnormally thin and short and it is not known whether they are capable of restoring conduction. A previous investigation was inconclusive4. Because of the physiological and clinical importance of this problem, we have now examined conduction serially through the lesion induced by the direct microinjection of lysophosphatidyl choline (LPC) into the cat spinal cord5. This lesion has the advantage that the phases of active demyelination and remyelination are well separated, thus permitting a reasonable correlation of the morphological with the physiological changes. We have found that secure conduction is restored with remyelination.