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. 2012:2012:295167.
doi: 10.1155/2012/295167. Epub 2012 Nov 20.

Conditioned medium from adipose tissue-derived mesenchymal stem cells induces CD4+FOXP3+ cells and increases IL-10 secretion

Ekaterina Ivanova-Todorova  1 , Ivan Bochev, Rumen Dimitrov, Kalina Belemezova, Milena Mourdjeva, Stanimir Kyurkchiev, Plamen Kinov, Iskra Altankova, Dobroslav Kyurkchiev
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Conditioned medium from adipose tissue-derived mesenchymal stem cells induces CD4+FOXP3+ cells and increases IL-10 secretion

Ekaterina Ivanova-Todorova et al. J Biomed Biotechnol. 2012.

Abstract

Mesenchymal stem cells (MSCs) are a new and promising tool for therapy of autoimmune disorders. In recent years their possibility to take part in the modulation of the immune response is discussed. The exact mechanisms for immunoregulation realized by MSCs are not clear yet, but interactions with other immunoregulatory cells may be involved in this process. The investigation of the influence of MSCs on the expression of FoxP3 and cytokine secretion by T helper cells was the aim of this study. T helper cells were isolated from PBMCs by magnetic separation and MSCs were isolated from human adipose tissue, and CD4⁺ T cells were cultured with conditional medium of MSCs. The methods which were used include flow cytometry, ELISA, and Human Proteome profiler kits. The results demonstrated that secretory factors in MSCs conditional medium lead to increased expression of FoxP3 and increased secretion of IL-10 by T helpers. The obtained results give us opportunity to discuss the interaction between two kinds of immunoregulatory cells: MSCs and FoxP3⁺ T helpers. We suppose that this interaction leads to increased number of immunosuppressive helpers which secrete IL-10. MSCs provide some of their immunosuppressive functions acting on T regulatory cells, and we believe that IL-6 secreted by MSCs is involved in this process.

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Figures

Figure 1
Figure 1
A representative dot plot showing the expression of CD25 and FoxP3 markers by T helpers. Panels (a) and (b) show the homogeneity of the purified CD4+ population; (c) shows the percentage of FoxP3+ cells in control culture; (d) shows an increase of the percentage of cells expressing FoxP3 after being cultured in AT-MSCs conditioned medium.
Figure 2
Figure 2
Cytokine secretion by CD4+ T lymphocytes cultured in AT-MSCs conditioned medium or control DMEM medium. Cultivation of CD4+ T cells in AT-MSCs conditioned medium did not induce changes in the secretion of TGFβ (a), IFNγ (b), or IL-2 (c). In contrast the secretion of IL-10 was statistically significantly upregulated (*P < 0.05) in the presence of AT-MSCs conditioned medium compared with the control (d). Mean values ± SD of 12 independent experiments with cells from different donors are shown.
Figure 3
Figure 3
Cytokines and chemokines found to be present at significant levels in AT-MSCs conditioned medium (black columns) compared to control DMEM medium (grey columns). The figure represents only the cytokines and chemokines which are known to affect T helper activities.
Figure 4
Figure 4
A possible indirect mechanism of the immunoregulatory effects of factors secreted by AT-MSCs.
See this image and copyright information in PMC

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