Foster G A, Stringer B M
Cardiff School of Biosciences, University of Wales, UK.
Brain Pathol. 1999 Jul;9(3):547-67. doi: 10.1111/j.1750-3639.1999.tb00541.x.
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.
对神经细胞进行基因操作在基础生物学和医学领域均具有优势。其效用使人们对神经元在胚胎发育期间及之后的存活、连接性和化学表型的调控方式有了更清晰的认识。这一成果很大程度上得益于近期通过基因手段生成了可重复且具有代表性的前体细胞供应，随后可在各种模式下对其进行分析。此外，神经退行性疾病移植临床应用方面取得的进展，引发了对用于移植的丰富、有效且安全的神经细胞供应的需求。本综述描述了基因方法如何与表观遗传手段相结合，被有利地用于实现这一目标。特别是，我们详细阐述了基因转移技术如何得以发展，以实现细胞永生化、细胞分化和定向的操控，以及出于纯化或安全目的对细胞进行可控选择。此外，现在还能够对细胞表面的抗原呈递进行基因改造。最后，详细介绍了利用神经细胞作为精巧的递送载体，将治疗性产物转移至中枢神经系统（CNS）的离散部位。总之，一旦对神经细胞生成、分化和死亡的表观遗传和基因控制得到更充分的确定，提供兼具固定元件和更灵活表达特征的混合物就变得可行。优化这两个控制系统的作用和相互作用应能改善用于神经移植的细胞供应。
