Amyotrophic lateral sclerosis (ALS) remains a fatal, neurodegenerative disease frequently leading to dysarthria and impaired swallowing. Better understanding of ALS pathophysiology is prompting the use of humoral cell therapies. Hence, a repeated cellular therapy was applied to ALS patients as an attempt to prevent speech deterioration. Autologous bone marrow-derived lineage-negative (Lin⁻) cells were intrathecally administered three times at six-week intervals to 42 sporadic ALS patients. Patients were examined for articulatory functions using subjective (VHI) and objective (FDA) scales. Selected trophic, proinflammatory factors and expression profiles of miRNA were measured in cerebrospinal fluid (CSF) and plasma by multiplex Luminex and q-PCR in different timepoints. Of the 42 patients who received the Lin⁻ cells, 6 showed improvement in articulatory functions, 27 remained stable, and 9 deteriorated after 18 weeks of therapy according to FDA scale. Clinical improvement was particularly evident by the 7^th day of each cell application and concerned better cough and swallow reflex, soft palate, laryngeal time, pitch, and volume. These results correlated with significant changes in the concentration of various trophic and proinflammatory factors and miRNA expression profiles. A multiple application of Lin⁻ cells proved to be safe and feasible. The repeated procedure can potentate a humoral effect and prevent speech deterioration. A short-lasting trophic effect of each Lin⁻ cells administration was observed on local and systemic level. However, further in-depth studies are necessary to sustain the beneficial effect.

中文翻译：

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反复谱系阴性干细胞/祖细胞给药对ALS患者关节功能的体液影响

肌萎缩性侧索硬化症（ALS）仍然是致命的神经退行性疾病，经常导致构音障碍和吞咽障碍。对ALS病理生理学的更好理解正在促进体液细胞疗法的使用。因此，为了防止语音恶化，对ALS患者进行了反复的细胞疗法。自体骨髓衍生的谱系阴性（林^- ）细胞在6周的间隔进行了鞘内施用三次，以42名散发性ALS患者。使用主观（VHI）和客观（FDA）量表检查患者的关节功能。通过多重Luminex和q-PCR在不同时间点测量脑脊液（CSF）和血浆中所选的营养，促炎因子和miRNA的表达谱。在接受林的42例患者中⁻根据FDA等级，在治疗18周后，有6个细胞的关节功能得到改善，其中27个保持稳定，其中9个细胞退化。每次使用细胞后的^第7天，临床改善尤为明显，并涉及更好的咳嗽和吞咽反射，软soft，喉时间，音调和体积。这些结果与各种营养和促炎因子的浓度以及miRNA表达谱的显着变化相关。林的多个应用程序^-细胞被证明是安全可行的。重复该过程可以增强体液效果并防止语音恶化。每个林的短时营养作用^-在局部和全身水平观察到细胞施用。但是，需要进一步深入研究以保持有益效果。