Effects of Educated Monocytes with Xenogeneic Mesenchymal Stem Cell-Derived Conditioned Medium in a Mouse Model of Chronic Asthma

Immunol Invest. 2018 Jul;47(5):504-520. doi: 10.1080/08820139.2018.1458108. Epub 2018 Apr 19.

Abstract

Background: This study was conducted to determine the potential of the monocytes educated with rat bone marrow mesenchymal stem cell-derived conditioned medium (MCM) in ameliorating animal model of asthma.

Methods: Chronic asthma was induced in the BALB/c mice using ovalbumin (OVA) sensitization. The monocytes were isolated from blood of mice and supplemented with 50% MCM or negative control media. After 24 h, the cells were designated as "non-educated or educated". Fourteen weeks after the onset of the study, animals were treated with educated or non-educated monocytes twice with a 1-week interval.

Results: The educated monocytes showed a reduction in the potential production of the respiratory burst and nitric oxide and the secretion of IL-12 and IL-4 compared to non-educated monocytes. Conversely, these monocytes exhibited a significant increase in the production of IL-10 and TGF-?. Also, the levels of CD68+/CD206+ cells significantly increased in the population of educated monocytes. More importantly, the severity of histopathological lesions, NF-?B p65 mRNA level in lung tissues, total serum IgE and the total cell count, as well as the eosinophil count in the bronchoalveolar lavage fluid, were significantly decreased in OVA-inhaled mice treated with educated monocytes compared to OVA-sensitized group receiving non-educated monocytes. With no advantage in up-regulation of Foxp3 Treg cells, the treatment with educated monocytes reduced the secretion of IL-5 and IL-13 by splenocytes of asthma mice more than splenocytes of the asthma mice treated with non-educated monocytes.

Conclusion: The educated monocytes with MCM may be as a promising strategy for cell-based therapies of asthma.

Keywords: Asthma; conditioned medium; mesenchymal stem cells; monocyte therapy.

MeSH terms

  • Animals
  • Asthma / etiology*
  • Asthma / metabolism*
  • Asthma / therapy
  • Bronchoalveolar Lavage Fluid / immunology
  • Cell- and Tissue-Based Therapy
  • Chronic Disease
  • Culture Media, Conditioned / pharmacology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Monocytes / drug effects*
  • Monocytes / physiology*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Respiratory Burst
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism

Substances

  • Culture Media, Conditioned
  • Cytokines
  • NF-kappa B
  • Nitric Oxide
  • Immunoglobulin E