Humoral Influence of Repeated Lineage-Negative Stem/Progenitor Cell Administration on Articulatory Functions in ALS Patients

Abstract

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 7th 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.

Evidence of Stem Cells Mobilization in the Blood of Patients with Pancreatitis: A Potential Link with Disease Severity

“…The results of multiple clinical trials using BMSCs strongly suggest their important role in the process of tissue healing and regeneration [25,26]. These observations led to further application of BMSCs in the treatment of some diseases, including systemic and local treatment of inflammatory bowel disease [27] or neurological and heart disorders [25,28]. The phenomenon of BMSC mobilization and its role in tissues was also assessed in some oncological disorders, including animal studies on gastric cancer [14,15], and in patients with pancreatic cancer [2,12].…”

Critical factors responsible for the therapeutic effect of mesenchymal stem/stromal cells in central nervous system disorders

“…The improvement correlated with the neurotrophin release. The transient therapeutic effect indicated the injected cells death, and traced to the necessity to repeat the cell-based therapy to maintain its effect [30]. We have analysed CSF from two groups of patients (adults suffering from ALS and children suffering from drug-resistant autoimmune epilepsy) treated intrathecally with ADRC three times, every three months.…”