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

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Abstract

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.

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.

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Fig. 1: Characterization of unstimulated MSCs (ALS and HC) and MSCs treated with proinflammatory cytokines (ALSc and HCc).
Fig. 2: Effect of MSCs on IL-10 and TNF-α production by PBMCs stimulated with LPS.
Fig. 3: Effect of MSCs on the percentage of activated CD4+ and CD8+ T lymphocytes.
Fig. 4: Influence of MSCs on the percentage of Th1 lymphocytes and production or expression of IFN-γ.
Fig. 5: Effect of MSCs on the percentage of Th2 lymphocytes and production or expression of IL-10.
Fig. 6: Effect of MSCs on the percentage of CD4+FOXP3+ T cells and Th17 lymphocytes and expression of IL-17 gene.

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Abbreviations

ALS:

amyotrophic lateral sclerosis

APC:

allophycocyanin

BM:

bone marrow

DMEM:

Dulbecco’s modified Eagle’s medium

DMSO:

dimethyl sulfoxide

ELISA:

enzyme-linked immunosorbent assay

FITC:

fluorescein isothiocyanate

HC:

healthy control

IFN:

interferon

IL:

interleukin

LPS:

lipopolysaccharide

mAb:

monoclonal antibody

MS:

multiple sclerosis

MSCs:

mesenchymal stem cells

PBMCs:

peripheral blood mononuclear cells

PBS:

phosphate-buffered saline

PD-L1:

programmed death-ligand 1

PE:

phycoerythrin

PHA:

phytohemagglutinin

RA:

rheumatoid arthritis

Th:

T helper

TNF:

tumour necrosis factor

Treg:

T regulatory

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Acknowledgements

This work was supported by Charles University grant (SVV 244-260435), by the Grant Agency of Charles University (projects number 80815 and 1516218) and by the Czech Ministry of Education, Youth and Sports (NPUI: LO1309 and LO1508).

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Authors and Affiliations

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

    Eliska Javorkova, Nicole Matejckova, Alena Zajicova, Barbora Hermankova, Michaela Hajkova, Pavla Bohacova, Jan Kossl, Magdalena Krulova & Vladimir Holan

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

    Eliska Javorkova, Nicole Matejckova, Barbora Hermankova, Michaela Hajkova, Pavla Bohacova, Jan Kossl, Magdalena Krulova & Vladimir Holan

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  1. Eliska Javorkova
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  2. Nicole Matejckova
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  3. Alena Zajicova
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  4. Barbora Hermankova
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  5. Michaela Hajkova
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  6. Pavla Bohacova
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  7. Jan Kossl
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  8. Magdalena Krulova
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  9. Vladimir Holan
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Correspondence to Eliska Javorkova.

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Javorkova, E., Matejckova, N., Zajicova, A. et al. Immunomodulatory Properties of Bone Marrow Mesenchymal Stem Cells from Patients with Amyotrophic Lateral Sclerosis and Healthy Donors. J Neuroimmune Pharmacol 14, 215–225 (2019). https://doi.org/10.1007/s11481-018-9812-7

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  • DOI: https://doi.org/10.1007/s11481-018-9812-7

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