MYELINATION FOLLOWING TRANSPLANTATION OF EGF-RESPONSIVE NEURAL STEM-CELLS INTO A MYELIN-DEFICIENT ENVIRONMENT

Epidermal growth factor (EGF)-responsive stem cells have been identifi ed in the murine central nervous system. These cells can be isolated f rom the brain and maintained in an undifferentiated state in vitro in the presence of EGF. After removing EGF, the cells cease mitosis and c an be induced to differentiate into neurons, astrocytes, and oligodend rocytes. We demonstrate that when the undifferentiated stem cells (nes tin-positive) are injected into the myelin-deficient rat spinal cord, they respond to cues within the mutant CNS and differentiate into myel inating oligodendrocytes, in contrast to their behavior in vitro, wher e they mainly form astrocytes. The cells provide a valuable model syst em for the study of the development of early oligodendrocytes from mul tipotent neural stem cells. Because these cells are influenced to divi de using growth factors, rather than oncogenes, and because they appea r to make appropriate lineage decisions when transplanted into a mutan t environment, they may provide an excellent source of cells for a var iety of future therapies using cellular transplantation. (C) 1997 Acad emic Press.