Lin Chun-Fu, Chen Yu-Hui, Yeh Chang-Ching, Hsu Sanford P C, Fu Yu-Show
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
Stem Cell Res Ther. 2025 Jul 22;16(1):395. doi: 10.1186/s13287-025-04485-1.
Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by progressive degeneration of motor neurons in the cerebral cortex, brainstem, and spinal cord, eventually leading to paralysis, respiratory failure, and death. Currently, no effective treatment exists for ALS.
This study examined the therapeutic potential of human umbilical cord mesenchymal stromal cells (HUMSCs) by transplanting 2 × 10⁶ HUMSCs into the spinal canal of transgenic mice expressing mutant human superoxide dismutase 1 (SOD1) at 8 weeks of age.
Survival analysis showed that the SOD1 group lived up to 171 days, while the SOD1 + HUMSCs group survived up to 199 days, extending lifespan by 17 days on average. Motor function tests, including rotarod performance, grip strength, open field activity, and balance beam tests, demonstrated that while the SOD1 group experienced progressive decline, the SOD1 + HUMSCs group showed improvement. Electrophysiological assessments at 20 weeks of age revealed weak muscle action potential in the SOD1 group, whereas the SOD1 + HUMSCs group exhibited noticeable improvements. Histological analysis indicated significant spinal cord atrophy in the SOD1 group, while HUMSCs transplantation mitigated this degeneration. Moreover, HUMSCs reduced blood-spinal cord barrier leakage and T lymphocyte infiltration, alleviating inflammation. The number and size of activated microglia and astrocytes increased in the SOD1 group but were reduced with HUMSCs treatment. Additionally, HUMSCs preserved more motor neurons in the anterior horns.
Collectively, transplantation of HUMSCs effectively reduced inflammatory reaction in spinal cord, decreased loss of neurons, ameliorated disease deterioration, and extended life span, suggesting that it could serve as a new direction of ALS treatment to improve patients' quality of life or behavioral function.
肌萎缩侧索硬化症（ALS）是一种运动神经元疾病，其特征是大脑皮层、脑干和脊髓中的运动神经元进行性退化，最终导致瘫痪、呼吸衰竭和死亡。目前，尚无针对ALS的有效治疗方法。
本研究通过在8周龄时将2×10⁶人脐带间充质基质细胞（HUMSCs）移植到表达突变型人超氧化物歧化酶1（SOD1）的转基因小鼠的椎管内，来研究HUMSCs的治疗潜力。
生存分析表明，SOD1组存活至171天，而SOD1 + HUMSCs组存活至199天，平均延长寿命17天。运动功能测试，包括转棒试验、握力、旷场活动和平衡木试验，表明SOD1组病情逐渐恶化，而SOD1 + HUMSCs组则有所改善。20周龄时的电生理评估显示，SOD1组肌肉动作电位较弱，而SOD1 + HUMSCs组有明显改善。组织学分析表明，SOD1组脊髓明显萎缩，而HUMSCs移植减轻了这种退化。此外，HUMSCs减少了血脊髓屏障渗漏和T淋巴细胞浸润，减轻了炎症。SOD1组中活化的小胶质细胞和星形胶质细胞的数量和大小增加，但HUMSCs治疗使其减少。此外，HUMSCs在前角保留了更多的运动神经元。
总体而言，HUMSCs移植有效减轻了脊髓炎症反应，减少了神经元损失，改善了疾病恶化，并延长了寿命，表明它可以作为改善ALS患者生活质量或行为功能的新治疗方向。
