Genetic regulatory elements introduced into neural stem and progenitor cell populations.
The genetic manipulation of neural cells has advantage in both basic biology and medicine. Its utility has provided a clearer understanding of how the survival, connectivity, and chemical phenotype of neurones is regulated during, and after, embryogenesis. Much of this achievement has come from the recent generation by genetic means of reproducible and representative supplies of precursor cells which can then be analyzed in a variety of paradigms. Furthermore, advances made in the clinical use of transplantation for neurodegenerative disease have created a demand for an abundant, efficacious and safe supply of neural cells for grafting. This review describes how genetic methods, in juxtaposition to epigenetic means, have been used advantageously to achieve this goal. In particular, we detail how gene transfer techniques have been developed to enable cell immortalization, manipulation of cell differentiation and commitment, and the controlled selection of cells for purification or safety purposes. In addition, it is now also possible to genetically modify antigen presentation on cell surfaces. Finally, there is detailed the transfer of therapeutic products to discrete parts of the central nervous system (CNS), using neural cells as elegant and sophisticated delivery vehicles. In conclusion, once the epigenetic and genetic controls over neural cell production, differentiation and death have been more fully determined, providing a mixture of hard-wired elements and more flexibly expressed characteristics becomes feasible. Optimization of the contributions and interactions of these two controlling systems should lead to improved cell supplies for neurotransplantation.
Cardiff School of Biosciences, University of Wales, UK. FosterGA@Cardiff.ac.uk
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D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D002469:Cell Separation; D018014:Gene Transfer Techniques; D005809:Genes, Regulator; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D006085:Graft Survival; D006801:Humans; D051379:Mice; D009474:Neurons / Q000166:cytology*; D010641:Phenotype; D051381:Rats; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D014162:Transfection