Use of Conditionally Immortalized Neural Progenitors for Transplantation and Gene Transfer to the CNS
Cell transplantation offers interesting possiblities for gene transfer to the CNS in that the cells can be genetically modified prior to grafting and thus used as carriers for transgenes that endow the grafted cells with properties that may be of therapeutic value. Initial studies along these lines have used genetically engineered fibroblasts (Fisher et al. 1991; Kawaja and Gage 1991; Kawaja et al. 1992; Dekker et al. 1994) or muscle cells (Jiao et al. 1993). Established cell lines, such as NIH 3T3 cells and C6 glioma, have also been used for this purpose, but they are of limited use due to their uncontrolled growth in the brain (Rosenberg et al. 1988; Uchida et al. 1989: Stromberg et al. 1990; Horellou et al. 1990a, b). Successful application of this cell-based gene therapy approach will depend on the identification of suitable cells that can serve as carriers for a wide range of potentially therapeutic transgenes and provide platforms for functionally efficient expression and secretion of transgene products. Such cells should ideally be brain-derived, homogeneous, and available in large quantities. To allow stable genetic modification, e.g., by use of retroviral vectors or techniques for homologous recombination, the cells should have the capacity to proliferate in vitro and possess suitable properties for subcloning of the transduced cells. Moreover, they should survive well over extended time periods after transplantation to the adult CNS; they should become stably integrated with the host brain tissue without any perturbation of the graft site: and they should carry no risk of tumor formation or immunological rejection.
KeywordsNerve Growth Factor Glial Fibrillary Acidic Protein Neural Progenitor Nucleus Basalis Ibotenic Acid
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