Evaluation of the Safety and Efficacy of Repeated Mesenchymal Stem Cell Transplantations in ALS Patients by Investigating Patients' Specific Immunological and Biochemical Biomarkers

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is an incurable disease. There are vigorous attempts to develop treatments to reduce the effects of this disease, and among these treatments is the transplantation of stem cells. This study aimed to retrospectively evaluate a mesenchymal stem cell (MSC) therapy cohort as a promising novel treatment modality by estimating some additional new parameters, such as immunological and biochemical factors.

Methods: This study was designed as an open-label, one-arm cohort retrospective study to evaluate potential diagnostic biomarkers of repeated infusions of autologous-bone marrow-derived mesenchymal stem cells (BM-MSCs) in 15 confirmed patients with ALS, administered at a dose of 1 × 106 cells/kg BW with a one-month interval, in equal amounts in both an intravenous (IV) and intrathecal (IT) capacity simultaneously, via various biochemical (iron (Fe), ferritin, total-iron-binding capacity (TIBC), transferrin, and creatine kinase (CK)) and immunological parameters (tumor necrosis factor-alpha (TNF-α), neurofilament light chain (NFL), and glial-cell-derived neurotrophic factor (GDNF) levels, evaluated during the three-month follow-up period in serum and cerebrospinal fluid (CSF).

Results: Our study indicated that, in the case of immunological biomarkers, TNF-α levels in the CSF showed a significant decrease at month three after transplantation compared with levels at month zero, and the p-value was p < 0.01. No statistically significant changes were observed for other immunological as well as biochemical parameters and a p-value of p > 0.05.

Conclusions: These results can indicate the potential benefit of stem cell transfusion in patients with ALS and suggest some diagnostic biomarkers. Several studies are required to approve these results.

Keywords: ALS; BM-MSC; GDNF; creatine kinase; ferritin; tumor necrosis factor-alpha.

Figure 1

Schematic diagram of the immunological parameters through months in serum and the CSF (A,B): tumor necrosis factor-alpha (TNF-α); (C,D): neurofilament light chain (NFL); and (E,F): glial-cell-derived neurotropic factor (GDNF), respectively. In serum, tested three times (before, as month −1, and after 1 and 3 months of transplantation). In CSF, tested before (month 0), after 1, and 3 months after transplantation. Levels tested in ELISA kit, ** (p-value < 0.01). ng/mL; nanograms per milliliter. CSF; cerebrospinal fluid (CSF).

Figure 2

Schematic diagram of the biochemical serum levels during the study: (A) iron (Fe), (B) ferritin, (C) total iron binding capacity (TIBC), (D) transferrin (as percentage, %), and (E) creatine kinase (CK). The three times estimated were before (month −1) and after one month, as well as three months after transplantation. p-value > 0.05. µg/dL: microgram per deciliter; u/L: units of enzyme activity per liter; and ng/mL: nanograms per milliliter.