Viral Manipulation of Neural Stem/Precursor Cells

Neural stem/precursor cells (NPCs) are defined according to their ability to self-renew and differentiate into all the major cellular types of the central nervous system (CNS). They can survive and proliferate in defined culture conditions as spherical aggregates (neurospheres) for a virtually indefinite number of passages, while remaining phenotypically and karyotypically stable. Besides classical stem cell-based approaches for regenerative medicine, NPCs hold a great potential also as system for delivering secreted factors and/or therapeutic genes in vivo, after transplantation. Solid evidence exist that NPCs survive transplantation procedures within the host CNS, specifically migrate within the damaged tissue, and protect the nervous system from inflammatory and other forms of damage. Viral vectors constitute a versatile tool for manipulating and improving some of the NPC properties, including their migratory and differentiation capacities, thus allowing a number of different possible applications. In this chapter, we have described some of the methods for the preparation of NPCs, the production and titration of the lentiviral particles, and the viral-mediated manipulation of NPCs, both ex vivo in organotypic slice cultures, as well as in vivo.