AbstractPotential new approaches to central nervous system (CNS) dysfunction have been created by the convergence of neural progenitor and stem cell biology with gene therapy and repair. Neural progenitors can be maintained in a proliferative state in vitro through retroviral transduction of an immortalizing gene. The immobilized progenitors then appear to behave much like normal CNS stem cells and hence have been termed stem‐like cells. The ability to transplant clonally related neural progenitors that self‐renew in culture but, after transplantation to the brain, differentiate appropriately into neurons and gila, may not only facilitate developmental inquiries, but also circumvent the limitations of primary fetal tissue for neural grafting. These cells are homogenous, abundant, and well‐characterized. They may express therapeutic gene products intrinsically or be readily engineered ex vivo to do so their ability to integrate efficiently into germinal zones and to migrate make possible transplant techniques that ensure widespread engraftment. Exploiting the inherent properties of neural progenitors, which allow them to become integral members of normal structures throughout the host brain, may allow foreign gene products to be delivered in a sustained, direct, and perhaps regulated fashion without disturbing other neurobiological processes. Transplants of such stem‐like cells may make possible new strategies for gene therapy and repair of the CNS, including the replacement of degenerated cells, the engineering of donor cells to be resistant to toxins, the delivery of missing metabolic or other gene products, to the over‐expression of molecules, and the substitution of alternate metabolic pathways. These approaches appear to be successful in various mouse models of neurodegeneration. Such observation may also provide a paradigm for the therapeutic use of stem cells from other organ systems. © 1995 Wiley