Brüstle O
Department of Neuropathology, University of Bonn Medical Center, Germany.
Brain Pathol. 1999 Jul;9(3):527-45. doi: 10.1111/j.1750-3639.1999.tb00540.x.
The ability to isolate multipotential neuroepithelial precursor cells from the mammalian nervous system provides exciting perspectives for the in vitro analysis of early nervous system development and the generation of donor cells for neural repair. New models are needed to study the properties of these cells in vivo. Neural chimeras have revealed a remarkable degree of plasticity in the developmental potential of neuroepithelial precursor cells. Following transplantation into the cerebral ventricle of embryonic hosts, precursors derived from various brain regions and developmental stages participate in host brain development and undergo region-specific differentiation into neurons and glia. These findings indicate that in the developing nervous system, migration and differentiation of neural precursors cells are regulated to a large extent by extrinsic signals. Neural chimeras composed of genetically modified cells will permit the study of the molecular mechanisms underlying these guidance cues, which may eventually be exploited for cell replacement strategies in the adult brain. A key problem in neural transplantation is the availability of suitable donor tissue. Neural chimeras composed of embryonic stem (ES) cell-derived neurons and glia depict ES cells as a versatile and virtually unlimited donor source for neural repair. Generation of interspecies neural chimeras composed of human and rodent cells facilitates the translation of these advances into clinical strategies for human nervous system repair.
从哺乳动物神经系统中分离多能神经上皮前体细胞的能力，为早期神经系统发育的体外分析以及神经修复供体细胞的生成提供了令人兴奋的前景。需要新的模型来研究这些细胞在体内的特性。神经嵌合体揭示了神经上皮前体细胞发育潜能中显著程度的可塑性。将来自不同脑区和发育阶段的前体细胞移植到胚胎宿主的脑室后，它们会参与宿主脑发育，并经历区域特异性分化形成神经元和神经胶质细胞。这些发现表明，在发育中的神经系统中，神经前体细胞的迁移和分化在很大程度上受外在信号调控。由基因修饰细胞组成的神经嵌合体将有助于研究这些引导信号背后的分子机制，这些机制最终可能被用于成体脑的细胞替代策略。神经移植中的一个关键问题是合适供体组织的可获得性。由胚胎干细胞（ES）衍生的神经元和神经胶质细胞组成的神经嵌合体，将ES细胞描述为神经修复的一种通用且几乎无限的供体来源。由人和啮齿动物细胞组成的种间神经嵌合体有助于将这些进展转化为人类神经系统修复的临床策略。
