Thonhoff Jason R, Ojeda Luis, Wu Ping
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555-0620, USA.
Curr Stem Cell Res Ther. 2009 Sep;4(3):178-99. doi: 10.2174/157488809789057392.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the selective loss of both spinal and upper motor neurons. One strategy in treating ALS is to use stem cells to replace lost spinal motor neurons. However, transplanted stem cell-derived motor neurons may not survive when exposed to the harsh microenvironment in the spinal cord of ALS. In particular, dysfunctional astrocytes and overactivated microglia in ALS may limit the survival of motor neurons generated from cell replacement therapy. On the other hand, stem cells may provide large quantities of motor neurons that can be used for studying glia-mediated toxic mechanisms and potential therapies in ALS. Here we will review methods and molecular factors for directed differentiation of stem cells into spinal motor neurons, the potential uses of these models for dissecting the mechanisms underlying glia-induced motor neuron degeneration and screening for new therapeutics aimed at protecting motor neurons in ALS, as well as discuss challenges facing the development of motor neuron replacement-based cell therapies for recovery in ALS.
肌萎缩侧索硬化症（ALS）是一种由脊髓和上运动神经元选择性丧失引起的神经退行性疾病。治疗ALS的一种策略是使用干细胞替代丢失的脊髓运动神经元。然而，移植的干细胞衍生的运动神经元在暴露于ALS脊髓中的恶劣微环境时可能无法存活。特别是，ALS中功能失调的星形胶质细胞和过度激活的小胶质细胞可能会限制细胞替代疗法产生的运动神经元的存活。另一方面，干细胞可以提供大量的运动神经元，可用于研究胶质细胞介导的毒性机制和ALS的潜在治疗方法。在这里，我们将回顾干细胞定向分化为脊髓运动神经元的方法和分子因素，这些模型在剖析胶质细胞诱导的运动神经元变性机制以及筛选旨在保护ALS中运动神经元的新疗法方面的潜在用途，并讨论基于运动神经元替代的细胞疗法在ALS恢复方面发展所面临的挑战。
