Use of Genetically Modified Cells to Deliver Neurotrophic Factors and Neurotransmitters to the Brain

Publisher Summary This chapter discusses the use of genetically modified cells to deliver neurotrophic factors and neurotransmitters to the brain. The strategy of using living cells as vehicles for delivering compounds to the central nervous system (CNS) has been pursued with great interest since the demonstrations in 1979 that fetal substantia nigra neurons grafted into the rat brain could functionally replace the neurotransmitter dopamine. This chapter describes some of the techniques involved in creating, characterizing, and using genetically modified cells as a method for delivering compounds to the CNS. Two representative model systems illustrate some of the techniques used to assess the in vivo functioning of cells engineered to produce either a neurotrophic factor (NGF) or neurotransmitters (acetylcholine, dopamine). Although this strategy may be pursued with a variety of cell types, the focus in a study described in the chapter was on the use of primary cells (fibroblasts), rather than established cell lines, for genetic modification because the power of the technique can be fully realized only with a cell type that will survive noninvasively for prolonged periods in the CNS.