Influence of Lineage-Negative Stem Cell Therapy on Articulatory Functions in ALS Patients

Abstract

Introduction. Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disease, leading to loss of muscle strength and motor control. Impaired speech and swallowing lower the quality of life and consequently may induce acute respiratory failure. Bone marrow-derived stem and progenitor cells (SPCs) may be a valuable source of trophic factors. In this study, we assessed whether adjuvant cellular therapy could affect the levels of selected neurotrophins and proinflammatory factors in the cerebrospinal fluid (CSF) and subsequently prevent the deterioration of articulation. Materials and Methods. The study group consisted of 32 patients with sporadic ALS who underwent autologous lineage-negative (Lin−) stem cell intrathecal administration to the spinal canal. Lin− cells were aspirated from the bone marrow and isolated using immunomagnetic beads and a lineage cell depletion kit. Patients were examined for articulatory functions by means of the Voice Handicap Index (VHI) questionnaire and Frenchay Dysarthria Assessment (FDA). In parallel, we carried out the analysis of selected trophic and proinflammatory factors in CSF utilizing multiplex fluorescent bead-based immunoassays. Results. Of the 32 patients who received the Lin− progenitor cell therapy, 6 (group I) showed improvement in articulatory functions, 23 remained stable (group II), and 3 deteriorated (group III) on the 28th day. The improvement was particularly noticeable in a better cough reflex, laryngeal time, and dribble reflex. A statistically significant lower level of brain-derived neurotrophic factor (BDNF) was observed on day 0 in group I compared to group II. The CSF concentrations of C-reactive protein (CRP) in group I significantly decreased 7 days after Lin− SPC transplantation. On the contrary, a significant increase in the tumor necrosis factor receptor (TNF-R) level was confirmed among patients from group I with improvement of dribble and coughing reflex, tongue movements, and respiration on the 7th day, as well as on day 28 including dribble reflex solely. Conclusions. An application of Lin− stem cells could potentate the beneficial humoral effect. The prevention of deterioration of articulatory functions in ALS patients after applying adjuvant Lin− stem cell therapy seems to be promising. Although the procedure is safe and feasible, it requires further in-depth studies.

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

“…Lineage-negative stem/progenitor cell population and utilization of its ability to secrete neurotrophic factors under stress, protein-poor conditions in approach to moderate the ongoing neurodegeneration in CNS of ALS patients, have been a focus of our research team over the past several years. However, in our previous works, we have presented data obtained from the observation of Lin − cell influence on various aspects of the disease in sALS patients after a single administration procedure [ 15 , 17 , 18 ]. In previous experiments, we have confirmed that this cell's population constitutes a safe and feasible source of trophic support when administered intrathecally.…”

“…In previous experiments, we have confirmed that this cell's population constitutes a safe and feasible source of trophic support when administered intrathecally. Furthermore, we have found that single administration of cells exerts beneficial effects on articulatory functions, expressed particularly in better cough and dribble reflex as well as improved laryngeal time [ 18 ]. Therefore, in the presented study, we hoped to maintain this beneficial effect and to further explore the prognostic factors which correspond with better response to the therapy.…”

“…Our studies utilizing this cell population have proved that they constitute a safe and feasible route of trophic support not only when administered intrathecally but also into the coronary artery in patients with acute myocardial infarction [ 15 – 17 ]. In our previous publications regarding effects of a single intrathecal autologous stem/progenitor Lin − cell infusion in ALS patients, we have in fact observed that this form of intervention may influence neurotrophin secretion, immune modulation in CNS environment and, moreover, affect articulatory functions [ 15 , 17 , 18 ]. Therefore, in this study, we have aimed to assess whether triple repeated administration of Lin − cells could sustain these beneficial humoral effects and perhaps further prevent speech deterioration.…”

Articulation recovery in ALS patients after lineage-negative adjuvant cell therapy - preliminary report

“…In parallel, we carried out the analysis of selected trophic (BDNF, NT-3, NGF-β) and proinflammatory factors (TNF-α, TNF-R, CRP) in CSF in day 0 and on the 7 th day post injection. Obtained results have been already published 41 . We are currently conducting research on even larger cohort of ALS subjects with 3 consecutive LIN - cell administrations with a one-year follow-up period.…”