Department of General Pathology, Pomeranian Medical University, 70-111 Szczecin, Poland.
Department of Neurology, Pomeranian Medical University, 71-252 Szczecin, Poland.
Int J Mol Sci. 2020 Feb 6;21(3):1070. doi: 10.3390/ijms21031070.
Amyotrophic lateral sclerosis (ALS) remains a fatal disease with limited therapeutic options. Signaling via neurotrophins (NTs), neuroinflammation, and certain micro-RNAs are believed to play essential role in ALS pathogenesis. Lineage-negative stem/progenitor cells (Lin) were obtained from bone marrow of 18 ALS patients and administered intrathecally. Clinical assessment was performed using ALS Functional Rating Scale (FRSr) and Norris scale. Protein concentrations were measured in plasma and cerebrospinal fluid (CSF) by multiplex fluorescent bead-based immunoassay. Gene expression in nucleated blood cells was assessed using gene microarray technique. Finally, miRNA expression was analyzed using qPCR in CSF and plasma samples. We observed a significant decrease of C-reactive protein (CRP) concentration in plasma on the seventh day from the application of cells. Gene array results revealed decreased expression of gene sets responsible for neutrophil activation. Further analysis revealed moderate negative correlation between CRP level in CSF and clinical outcome. Brain-derived neurotrophic factor (BDNF) concentrations in both plasma and CSF significantly correlated with the favorable clinical outcome. On a micro-RNA level, we observed significant increase of miR-16-5p expression one week after transplantation in both body fluids and significant increase of miR-206 expression in plasma. Administration of Lin cells may decrease inflammatory response and prevent neurodegeneration. However, these issues require further investigations.
肌萎缩侧索硬化症（ALS）仍然是一种致命疾病，治疗选择有限。神经递质（NTs）、神经炎症和某些 microRNAs 的信号传递被认为在 ALS 的发病机制中起重要作用。从 18 名 ALS 患者的骨髓中获得无谱系阴性干细胞/祖细胞（Lin），并进行鞘内给药。使用肌萎缩侧索硬化功能评定量表（FRSr）和诺里斯量表进行临床评估。通过基于多重荧光珠的免疫测定法测量血浆和脑脊液（CSF）中的蛋白浓度。使用基因微阵列技术评估核血细胞中的基因表达。最后，使用 qPCR 分析 CSF 和血浆样本中的 miRNA 表达。我们观察到从细胞给药后第 7 天，血浆中 C 反应蛋白（CRP）浓度显著下降。基因芯片结果显示，负责中性粒细胞激活的基因集表达下调。进一步分析显示，CSF 中 CRP 水平与临床结果呈中度负相关。血浆和 CSF 中的脑源性神经营养因子（BDNF）浓度与良好的临床结果显著相关。在 micro-RNA 水平上，我们观察到移植后一周两种体液中 miR-16-5p 表达显著增加，血浆中 miR-206 表达显著增加。Lin 细胞的给药可能会降低炎症反应并阻止神经退行性变。然而，这些问题需要进一步研究。
