Intraspinal delivery of neurotrophin-3 using neural stem cells geneticallymodified by recombinant retrovirus

Neural stem cells have been shown to participate in the repair of experimen tal CNS disorders. To examine their potential in spinal cord repair, we use d retroviral vectors to genetically modify a clone of neural stem cells, C1 7, to overproduce neurotrophin-3 (NT-3). The cells were infected with a ret rovirus construct containing the NT-3.IRES.lacZ/neo sequence and cloned by limiting dilution and selection for lacZ expression. We studied the charact eristics of the modified neural stem cells in vitro and after transplantati on into the intact spinal cord of immunosuppressed adult rats. Our results show that: (i) most of the genetically modified cells express both NT-3 and lacZ genes with a high coexpression ratio in vitro and after transplantati on; and (ii) large numbers of the xenografted cells survive in the spinal c ord of adult rats for at least 2 months, differentiate into neuronal and gl ial phenotypes, and migrate for long distances. We conclude that geneticall y modified neural stem cells, acting as a source of neurotrophic factors, h ave the potential to participate in spinal cord repair, (C) 1999 Academic P ress.