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Journal of Neuroimmune Pharmacology

, Volume 14, Issue 2, pp 215–225 | Cite as

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

  • Eliska JavorkovaEmail author
  • Nicole Matejckova
  • Alena Zajicova
  • Barbora Hermankova
  • Michaela Hajkova
  • Pavla Bohacova
  • Jan Kossl
  • Magdalena Krulova
  • Vladimir Holan
ORIGINAL ARTICLE

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.

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.

Keywords

Mesenchymal stem cells Amyotrophic lateral sclerosis Immunomodulation Helper T lymphocytes CD4+FOXP3+ T lymphocytes Proinflammatory cytokines 

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

Notes

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).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Eliska Javorkova
    • 1
    • 2
    Email author
  • Nicole Matejckova
    • 1
    • 2
  • Alena Zajicova
    • 1
  • Barbora Hermankova
    • 1
    • 2
  • Michaela Hajkova
    • 1
    • 2
  • Pavla Bohacova
    • 1
    • 2
  • Jan Kossl
    • 1
    • 2
  • Magdalena Krulova
    • 1
    • 2
  • Vladimir Holan
    • 1
    • 2
  1. 1.Department of Transplantation ImmunologyInstitute of Experimental Medicine of the Czech Academy of SciencesPragueCzech Republic
  2. 2.Department of Cell Biology, Faculty of ScienceCharles UniversityPrague 2Czech Republic

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