Immunomodulatory Properties of Bone Marrow Mesenchymal Stem Cells from Patients with Amyotrophic Lateral Sclerosis and Healthy Donors.

Pathogenesis of amyotrophic lateral sclerosis (ALS) involves several mechanisms resulting in a shift from a neuroprotective to a neurotoxic immune reaction. A promising tool for ALS treatment is represented by mesenchymal stem cells (MSCs), which possess both regenerative potential and immunomodulatory properties. In this study, we aimed to compare the immunomodulatory properties of MSCs isolated from the bone marrow of patients suffering from ALS and healthy donors. Moreover, the influence of proinflammatory cytokines on the immunoregulatory functions of MSCs was also evaluated. We found that MSCs from ALS patients and healthy donors comparably affected mitogen-stimulated peripheral blood mononuclear cells and reduced the percentage of T helper (Th)1, Th17 and CD8+CD25+ lymphocytes. These MSCs also equally increased the percentage of Th2 and CD4+FOXP3+ T lymphocytes. On the other hand, MSCs from ALS patients decreased more strongly the production of tumour necrosis factor-α than MSCs from healthy donors, but this difference was abrogated in the case of MSCs stimulated with cytokines. Significant differences between cytokine-treated MSCs from ALS patients and healthy donors were detected in the effects on the percentage of CD8+CD25+ and CD4+FOXP3+ T lymphocytes. In general, treatment of MSCs with cytokines results in a potentiation of their effects, but in the case of MSCs from ALS patients, it causes stagnation or even restriction of some of their immunomodulatory properties. We conclude that MSCs from ALS patients exert comparable immunomodulatory effects to MSCs from healthy donors, but respond differently to stimulation with proinflammatory cytokines. Graphical Abstract Treatment of mesenchymal stem cells (MSCs) with cytokines results in a potentiation of their effects, but in the case of MSCs from amyotrophic lateral sclerosis (ALS) patients, it causes stagnation (an equal reduction of the percentage of CD8+CD25+ T lymphocytes) or even restriction (no increase of proportion of CD4+FOXP3+ T lymphocytes) of some of their immunomodulatory properties. It means that MSCs from ALS patients exert comparable immunomodulatory effects to MSCs from healthy donors, but respond differently to stimulation with proinflammatory cytokines.

Characterisation of mesenchymal stem cells from patients with amyotrophic lateral sclerosis.

AIMS: Mesenchymal stem cells (MSCs) have recently been tested in clinical trials to treat severe diseases, including amyotrophic lateral sclerosis (ALS). Since autologous MSCs are frequently used for therapy, we aimed to evaluate the possible influence of the disease on characteristics and function of these cells. METHODS: MSCs were isolated from the bone marrow of patients with ALS and compared with MSCs from healthy controls (HC). The cells were tested for phenotype, growth properties, differentiation ability, metabolic activity, secretory potential, expression of genes for immunomodulatory molecules and for the ability to regulate proliferation of mitogen-stimulated peripheral blood leucocytes. MSCs from patients with ALS and HC were either unstimulated or treated with proinflammatory cytokines for 24 hours before testing. RESULTS: MSCs isolated from patients with ALS have a higher differentiation potential into adipocytes, express elevated levels of mRNA for interleukin-6, but produce less hepatocyte growth factor than MSCs from HC. On the other hand, there were no significant differences between MSCs from patients with ALS and HC in the expression of phenotypic markers, growth properties, metabolic activity, osteogenic differentiation potential and immunoregulatory properties. CONCLUSIONS: The results suggest that, in spite of some differences in cytokine production, MSCs from patients with ALS can be useful as autologous cells in therapy of ALS.