Kawaja M D, Ray J, Gage F H
Department of Neurosciences, University of California, San Diego, La Jolla 92093.
Genet Eng (N Y). 1991;13:205-20. doi: 10.1007/978-1-4615-3760-1_9.
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.
对原代表皮成纤维细胞进行基因改造，为向受损或患病的中枢神经系统局部递送缺陷性递质特异性酶（如酪氨酸羟化酶）或营养物质（如神经生长因子）提供了一种新方法。尽管成纤维细胞无法对有缺陷的神经连接进行解剖学矫正，但它们可以在体内充当酶和生长因子的生物泵。基因工程细胞改善中枢神经系统疾病动物模型中疾病表型的能力最终可能导致功能恢复。目前，原代表皮成纤维细胞似乎是用于帕金森病动物模型的基因转移和脑内移植的便利细胞群体。对于未来的研究而言，提供有关脑内植入后转基因产物（如酪氨酸羟化酶）长期稳定表达的数据，以及确定移植到神经系统中的原代细胞存活的最佳条件，现在至关重要。
