| Neuronal progenitor cells (NPCs) residing in the adult brain are attractive candidates for isolation, in vitro expansion, and autologous transplantation to replace neurons lost to neurodegenerative disease, stroke and traumatic brain injury. The viability of using adult NPCs as therapeutic grafts ultimately will be determined by their capacity for in vitro expansion, to numbers sufficient for grafting, and by their neurogenic potential after transplantation to diverse brain environments. These studies explored the neurogenic potential of transplanted adult NPCs, which were expanded from the subependymal zone, a known site of neurogenesis in the adult brain. Cells were implanted in a neurogenic site, a non-neurogenic site and an injured, non-neurogenic site. Results demonstrate that adult SEZ NPCs are capable of metadifferentiation to hippocampal granule cell neurons following transplantation to the adult dentate gyrus, a neurogenic environment. Cells were also transplanted to the classically non-neurogenic striatum in an animal model of Parkinson's Disease. Cells did not differentiate to neurons in the normal or deafferented striatum, even when neuronal differentiation of a subset of cells was induced in vitro prior to transplantation. However, grafts did prevent behavioral decline in hemiparkinsonian rats, possibly due to functional effects of the large amount of undifferentiated cells that survived in the grafts. These novel findings support further study of expanded adult SEZ NPCs for potential autologous grafting in the injured adult brain. |
