Lang Kenneth J D, Rathjen Joy, Vassilieva Svetlana, Rathjen Peter D
School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia.
J Neurosci Res. 2004 Apr 15;76(2):184-92. doi: 10.1002/jnr.20036.
The many and varied proposed applications of cell replacement therapies in the treatment of human disease states, particularly those arising from cell loss or dysfunction, have been discussed widely in both the scientific and popular press. Although an attractive concept, cell therapies require the development of a readily available source of donor cells suitable for transplantation. Embryonic stem (ES) cells, with proven ability to differentiate to all cell populations of the embryo and adult in vitro, provide a potential source of therapeutic cells. The differentiation capability of mouse ES cells in vitro has been studied extensively over the last 20 years and the formation of neural precursors and neural cell lineages from mouse ES cells is well established. Cell populations highly enriched/homogenous in neural precursors have been achieved using a variety of chemical or biological inducing agents coupled with selective growth conditions. Preliminary reports suggest that similar neural enrichment is seen when these methodologies are applied to primate and human ES cells. ES cell-derived neural precursors have been analyzed in vitro and in vivo and found to be functionally normal and, after introduction into rodent models of human neurodegenerative diseases, capable of effecting measurable disease recovery. We review progress in the formation of neural precursors from mouse ES cells, particularly the recent reports of directed differentiation of ES in response to biological inductive factors, and assess the transfer of these approaches to human ES cells.
细胞替代疗法在治疗人类疾病状态，尤其是那些由细胞丢失或功能障碍引起的疾病方面，有许多不同的应用提议，这在科学和大众媒体中都得到了广泛讨论。尽管细胞疗法是一个有吸引力的概念，但它需要开发一种易于获得的、适合移植的供体细胞来源。胚胎干细胞（ES细胞）在体外已被证明有能力分化为胚胎和成年个体的所有细胞群体，它提供了一种潜在的治疗细胞来源。在过去20年里，小鼠ES细胞在体外的分化能力得到了广泛研究，并且从小鼠ES细胞形成神经前体细胞和神经细胞谱系已经得到充分证实。使用各种化学或生物诱导剂并结合选择性生长条件，已经获得了高度富集/均一的神经前体细胞群体。初步报告表明，当这些方法应用于灵长类和人类ES细胞时，也能看到类似的神经富集现象。ES细胞来源的神经前体细胞已在体外和体内进行了分析，发现其功能正常，并且在被引入人类神经退行性疾病的啮齿动物模型后，能够实现可测量的疾病恢复。我们回顾了从小鼠ES细胞形成神经前体细胞的进展，特别是最近关于ES细胞在生物诱导因子作用下定向分化的报道，并评估了将这些方法应用于人类ES细胞的情况。
