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

Abstract

ABSTRACTBackground: 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.