Employment of fibroblasts for gene transfer: applications for grafting into the central nervous system.
Genetic modification of primary skin fibroblasts offers a new approach to the focal delivery of deficient transmitter-specific enzymes (e.g., TH) or trophic substances (e.g., NGF) to the damaged or diseased CNS. Although fibroblasts are unable to provide anatomical corrections to defective neural connectivity, they can serve as biological pumps for the enzymes and growth factors in vivo. The capability of genetically engineered cells to ameliorate disease phenotypes in animal models of CNS disorders may ultimately results in the restoration of function. At this time, primary skin fibroblasts appear to be a convenient cellular population for the application of gene transfer and intracerebral grafting for the animal model of Parkinson's disease. It is now important for future investigations to provide data concerning the long-term stable expression of the transgene product (e.g., TH) following intracerebral implantation, as well as determining optimal conditions for the survival of primary cells grafted into the nervous system.
Kawaja
M D
MD
Department of Neurosciences, University of California, San Diego, La Jolla 92093.
Ray
J
J
Gage
F H
FH
D000818:Animals; D002490:Central Nervous System / Q000378:metabolism* / Q000601:surgery; D005347:Fibroblasts / Q000378:metabolism* / Q000637:transplantation; D005818:Genetic Engineering; D015316:Genetic Therapy; D006801:Humans; D014162:Transfection