Naegele Janice R., Vemuri Mohan C., Studer Lorenz
Department of Biology, Wesleyan University, Middletown CT
Life Technologies, Frederick, MD 21704
Stem cell therapies for treating or curing severe neurological disorders and intractable epilepsy are envisioned for regenerative medicine and neurology of the future. Studies of how the human nervous system develops from stem cells are yielding clues for how to direct pluripotent stem cells into specific neural and glial fates. Reagents and protocols to grow human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in xenofree conditions are now available. Transgenic technology has been developed using Bacterial Artificial Chromosomes (BACs) to force transcription factor expression in these cell lines, making it feasible to direct ESCs and iPSCs toward neural fates to derive functionally distinct classes of neurons, oligodendrocytes and astrocytes comparable to the endogenous cells in different regions of the fetal brain and spinal cord. The remarkable progress in this field may lead to powerful new stem cell-based therapies for curing human neurological disorders and epilepsy. We review some of the major advantages of deriving specific cell types with this new technology, applications in basic research, and prospects for treating circuit abnormalities and intractable seizures in patients with epilepsy.
干细胞疗法用于治疗或治愈严重的神经系统疾病和顽固性癫痫,是未来再生医学和神经学所展望的方向。关于人类神经系统如何从干细胞发育而来的研究,正在为如何将多能干细胞定向分化为特定的神经和胶质细胞命运提供线索。现在已有在无动物源条件下培养人类胚胎干细胞(ESC)和诱导多能干细胞(iPSC)的试剂和方案。利用细菌人工染色体(BAC)开发了转基因技术,以促使这些细胞系中的转录因子表达,从而使将ESC和iPSC定向分化为神经细胞命运,以获得与胎儿脑和脊髓不同区域的内源性细胞相当的功能不同类型的神经元、少突胶质细胞和星形胶质细胞成为可能。该领域的显著进展可能会带来强大的基于干细胞的新疗法,用于治愈人类神经系统疾病和癫痫。我们回顾了利用这项新技术衍生特定细胞类型的一些主要优势、在基础研究中的应用,以及治疗癫痫患者电路异常和顽固性癫痫发作的前景。