Gene 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 actions in vivo have provided refined procedures for the gene transfer of bioactive molecules to the mammalian brain with the ability to interfere with neurodegenerative processes or stimulate repair. These new methodologies, when combined with behavioral in vivo studies to assess functional recovery, provide the framework for the development and characterization of gene transfer procedures that might be relevant for the design of future therapies to counteract degeneration in the mammalian brain. In this review we summarize recent evidence demonstrating the usefulness of immortalized neural stem cell lines for long-term and localized gene transfer to the brain, in particular in relation to the cellular and functional effects of gene transfer to trophic factors. Recent experimental evidence demonstrates that localized nerve growth factor supplements to discrete cholinergic nuclei can counteract age-associated cognitive impairments.