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.

Department of Cell Biology Faculty of Science Charles University Vinicna 7 128 43 Prague 2 Czech Republic

Department of Transplantation Immunology Institute of Experimental Medicine of the Czech Academy of Sciences Videnska 1083 4 142 20 Prague Czech Republic

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Amyotroph Lateral Scler Other Motor Neuron Disord. 2000 Dec;1(5):293-9 PubMed

Scand J Immunol. 2004 Sep;60(3):307-15 PubMed

Blood. 2005 Feb 15;105(4):1815-22 PubMed

Amyotroph Lateral Scler Other Motor Neuron Disord. 2004 Dec;5(4):213-9 PubMed

Cytotherapy. 2006;8(4):315-7 PubMed

Immunol Lett. 2007 Jun 15;110(2):91-100 PubMed

Cell Transplant. 2008;17(3):255-66 PubMed

Neurobiol Dis. 2008 Sep;31(3):395-405 PubMed

Exp Hematol. 2009 Dec;37(12):1445-53 PubMed

Stem Cells Dev. 2010 Jul;19(7):1035-42 PubMed

PLoS One. 2010 Feb 16;5(2):e9252 PubMed

J Immunol. 2010 Jul 1;185(1):302-12 PubMed

Arch Neurol. 2010 Oct;67(10):1187-94 PubMed

Stem Cells Dev. 2012 Apr 10;21(6):901-10 PubMed

Exp Neurol. 2012 Jan;233(1):472-80 PubMed

Curr Stem Cell Res Ther. 2012 Nov;7(6):407-14 PubMed

J Pathol. 2013 Jan;229(2):176-85 PubMed

Neuroepidemiology. 2013;41(2):118-30 PubMed

Cell Transplant. 2015;24(2):151-65 PubMed

Stem Cells Dev. 2014 Oct 15;23(20):2490-500 PubMed

Neurotherapeutics. 2015 Apr;12(2):364-75 PubMed

Thymus. 1989;14(1-3):43-53 PubMed

J Immunol Res. 2015;2015:284215 PubMed

Autoimmunity. 2016;49(2):124-31 PubMed

Stem Cell Rev. 2016 Dec;12(6):654-663 PubMed

N Engl J Med. 1994 Mar 3;330(9):585-91 PubMed