ISOLATION AND TRANSPLANTATION OF MULTIPOTENTIAL POPULATIONS OF EPIDERMAL GROWTH FACTOR-RESPONSIVE, NEURAL PROGENITOR CELLS FROM THE CANINE BRAIN

Glial cell transplantation into myelin-deficient rodent models has res ulted in myelination of axons and restoration of conduction velocity, The shaking (sh) pup canine myelin mutant is a useful model in which t o test the ability to repair human myelin diseases, but as in humans, the canine donor supply for allografting is limited, A solution may be provided by self-renewing epidermal growth factor (EGF)-responsive mu ltipotential neural progenitor cell populations (''neurospheres''), No nadherent spherical clusters, similar in appearance to murine neurosph eres, have been obtained from the brain of perinatal wildtype (wt) can ine brain and expanded in vitro in the presence of EGF for at least 6 months. Most of the cells in these clusters express a nestin-related p rotein, Within 1-2 weeks after removal of EGF, cells from the clusters generate neurons, astrocytes, and both oligodendroglial progenitors a nd oligodendrocytes. Transplantation of lacZ-expressing wt neurosphere s into the myelin-deficient (md) rat showed that a proportion of the c ells differentiated into oligodendrocytes and produced myelin, In addi tion, cells from the neurosphere populations survived at least 6 weeks after grafting into a 14-day postnatal sh pup recipient and at least 2 weeks after grafting into an adult sit pup recipient, Thus, neurosph eres provide a new source of allogeneic donor cells for transplantatio n studies in this mutant. (C) 1997 Wiley-Liss, Inc.