Abstract
Objective:Mesenchymal stem cells (MSCs), which possess immunosuppressive characteristics on induced T-cells, were shown to be applicable in prevention and treatment of graft-versus-host disease. However, knowledge of effective cell sources is still limited. In this study, MSCs from different human tissues, i.e. bone marrow (BM), Wharton’s jelly (WJ), and adipose tissue, were isolated, and the immune suppression of stimulated T cells was analyzed comparatively.Materials and Methods:MSCs were co-cultured with phytohemagglutinin-induced T-cells with co-culture techniques with and without cell-to-cell contact. After co-culture for 24 and 96 h, the proliferation rate of T cells was estimated by carboxyfluorescein succinimidyl ester and apoptosis by annexin V/PI methods. Both T cells and MSCs were analyzed with respect to gene expressions by real-time polymerase chain reaction and their specific protein levels by ELISA.Results:The results showed that all three MSC lines significantly suppressed T-cell proliferation; BM-MSCs were most effective. Similarly, T-cell apoptosis was induced most strongly by BM-MSCs in indirect culture. In T cells, the genes in NFkB and tumor necrosis factor pathways were silenced and the caspase pathway was induced after co-culture. These results were confirmed with the measurement of protein levels, like transforming growth factor β1, IL-6, interferon-γ, interleukin (IL)-2, and tumor necrosis factor-α. Additionally, IL-17A was detected in high levels in WJ-MSC co-cultures. We showed that IL-17A-producing Tregs are the key mediators in the treatment of graft-versus-host disease.Conclusion:BM-MSCs, which have been used in clinical applications for a while, showed the greatest immunosuppressive effect compared to other MSCs. However, a promising cell source could also be WJ, which is also effective in suppression with fewer ethical concerns. We described the molecular mechanism of WJ-MSCs in allogenic transplants for the first time.
Highlights
The crucial role of mesenchymal stem cells (MSCs) in tissue function is widely known with their effect on the tissue components by paracrine and autocrine factors
bone marrow (BM)-Mesenchymal stem cells (MSCs), which have been used in clinical applications for a while, showed the greatest immunosuppressive effect compared to other MSCs
We described the molecular mechanism of Wharton’s jelly (WJ)-MSCs in allogenic transplants for the first time
Summary
The crucial role of mesenchymal stem cells (MSCs) in tissue function is widely known with their effect on the tissue components by paracrine and autocrine factors. The molecular mechanisms underlying these effects are still unclear and need to be explored in much greater detail; they probably require both cell-to-cell contact and a variety of cytokines and soluble factors in a paracrine manner. The direct co-culture of MSCs was demonstrated to play an important role in their apoptotic effect in our recent study [11]. It was aimed both to characterize comparatively the immunosuppressive effects of MSCs derived from three different human tissues, i.e. BM, WJ, and AT, in detail and to clarify the mechanisms underlying them
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