Department of Neurology, College of Medicine, Hanyang University, #17 Haengdang-dong, Seongdong-gu, Seoul, 133-791, Republic of Korea.
Neurosci Lett. 2010 Jan 14;468(3):190-4. doi: 10.1016/j.neulet.2009.10.074. Epub 2009 Oct 29.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron loss. Although the underlying cause of the disease remains unclear, a variety of pathogenic mechanisms have been proposed. Despite promising preclinical studies showing the modification of the disease progression, most trials have failed to demonstrate any significant improvement in outcome. Stem cell therapy therefore has been proposed as an alternative therapy for ALS. In this study, we evaluated the dose-dependent effects of human bone marrow mesenchymal stem cells (hMSCs) obtained from an ALS patient (ALS-hMSCs) on SOD1 mice via intrathecal injection and showed its practicality for hMSCs. We transplanted different doses (1x10(4), 2x10(5), and 1x10(6)) of ALS-hMSCs into the cisterna magna and performed clinical observations including symptom onset, survival time, and locomotor performance using the rotarod test. Nissl staining was performed to evaluate motor neurons in lumbar spinal cord sections at 109 days, and transplanted cells were evaluated by immuno-fluorescence staining at the end stage. A cell dose of 1x10(6) cells significantly prolonged life span and delayed the decline of motor performance. At this dose, the average number of motor neurons was significantly higher than those of the untreated and 1x10(4) cell treated groups. Most injected hMSCs distributed in the ventricular system and subarachnoid space, while some migrated into the brain and spinal cord. These data suggest that intrathecal injection with an optimized cell number could be a potential route for stem cell therapy in ALS patients.
肌萎缩侧索硬化症（ALS）是一种进行性神经退行性疾病，其特征是运动神经元丧失。虽然该疾病的根本原因仍不清楚，但已经提出了多种发病机制。尽管有很有前景的临床前研究表明可以改变疾病进展，但大多数试验未能证明在结果上有任何显著改善。因此，干细胞疗法被提出作为 ALS 的一种替代疗法。在这项研究中，我们通过鞘内注射评估了来自 ALS 患者的人骨髓间充质干细胞（hMSCs）（ALS-hMSCs）的剂量依赖性作用，SOD1 小鼠，并展示了其在 hMSCs 中的实用性。我们将不同剂量（1x10(4)、2x10(5)和 1x10(6)）的 ALS-hMSCs 移植到枕骨大孔中，并通过旋转棒试验进行了包括症状发作、存活时间和运动性能在内的临床观察。在 109 天时，通过尼氏染色评估腰脊髓切片中的运动神经元，并在终末阶段通过免疫荧光染色评估移植细胞。1x10(6)个细胞的细胞剂量可显著延长寿命并延迟运动性能下降。在该剂量下，运动神经元的平均数量明显高于未治疗组和 1x10(4)个细胞处理组。大多数注入的 hMSCs 分布在脑室系统和蛛网膜下腔，而一些迁移到大脑和脊髓。这些数据表明，用优化的细胞数量进行鞘内注射可能是 ALS 患者干细胞治疗的一种潜在途径。
