CONE TRANSFER TO THE MAMMALIAN BRAIN USING NEURAL STEM-CELLS - A FOCUS ON TROPHIC FACTORS, NEUROREGENERATION, AND CHOLINERGIC NEURON SYSTEMS

Recent advances in stem cell biology, molecular neurobiology, and gene transfer in combination with our understanding of neurotrophic action s in vivo have provided refined procedures for the gene transfer of bi oactive molecules to the mammalian brain with the ability to interfere with neurodegenerative processes or stimulate repair. These new metho dologies, when combined with behavioral in vivo studies to assess func tional recovery, provide the framework for the development and charact erization of gene transfer procedures that might be relevant for the d esign of future therapies to counteract degeneration in the mammalian brain. In this review we summarize recent evidence demonstrating the u sefulness of immortalized neural stem cell lines for long-term and loc alized gene transfer to the brain, in particular in relation to the ce llular and functional effects of gene transfer of trophic factors. Rec ent experimental evidence demonstrates that localized nerve growth fac tor supplements to discrete cholinergic nuclei can counteract age-asso ciated cognitive impairments. (C) 1996 Wiley-Liss, Inc.