We have previously demonstrated that lineage negative cells (Lin(neg)) from umbilical cord blood (UCB) develop into multipotent cells capable of differentiation into bone, muscle, endothelial and neural cells. The objective of this study was to determine the optimal conditions required for Linn,g UCB cells to differentiate into neuronal cells and oligodendrocytes, We demonstrate that early neural stage markers (nestin, neurofilament, A2B5 and Sox2) are expressed in Lin(neg) cells Cultured in FGF4, SCF, Flt3-ligand reprogramming Culture media followed by the early macroglial cell marker O4. Early stage oligodendrocyte markers CNPase, GalC, Olig2 and the late-stage marker MOSP are observed, as is the Schwann cell marker PMP22. In summary, Lin(neg) UCB cells, when appropriately cultured, are able to exhibit characteristics of neuronal and macroglial cells that can specifically differentiate into oligodendrocytes and Schwann cells and express proteins associated with myelin production after in vitro differentiation. (C) 2008 Elsevier Inc. All rights reserved.