Polysialylated neural cell adhesion molecule-positive CNS precursors generate both oligodendrocytes and schwann cells to remyelinate the CNS after transplantation

Transplantation offers a means of identifying the differentiation and myeli nation potential of early neural precursors, features relevant to myelin re generation in demyelinating diseases. In the postnatal rat brain, precursor cells expressing the polysialylated (PSA) form of the neural cell adhesion molecule NCAM have been shown to generate mostly oligodendrocytes and astr ocytes in vitro (Ben-Hur et al., 1998). Immunoselected PSA-NCAM+ newborn ra t CNS precursors were expanded as clusters with FGF2 and grafted into a foc al demyelinating lesion in adult rat spinal cord. We show that these neural precursors can completely remyelinate such CNS lesions. While PSA-NCAM+ pr ecursor clusters contain rare P75+ putative neural crest precursors, they d o not generate Schwann cells in vitro even in the presence of glial growth factor. Yet they generate oligodendrocytes, astrocytes, and Schwann cells i n vivo when confronted with demyelinated axons in a glia-free area. We conf irmed the transplant origin of these Schwann cells using Y chromosome in si tu hybridization and immunostaining for the peripheral myelin protein P0 of tissue from female rats that had been grafted with male cell clusters. The number and distribution of Schwann cells within remyelinated tissue, and t he absence of P0 mRNAs in donor cells, indicated that Schwann cells were ge nerated by expansion and differentiation of transplanted PSA-NCAM+ neural p recursors and were not derived from contaminating Schwann cells. Thus, tran splantation into demyelinated CNS tissue reveals an unexpected differentiat ion potential of a neural precursor, resulting in remyelination of CNS axon s by PNS and CNS myelin-forming cells.