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.
In this study, analysis and comprehensive comparison of neurogenic differentiation capacity of human bursal tissuederived-stem cells (hBT-SCs) was aimed with human bone marrow derived mesenchymal stem cells (hBM-MSCs). hBT-SCs was isolated from subacromial bursa tissue (n ¼ 3) by collagen type-II digestion. The expression of stem cell markers, differentiation capacity and telomerase activity were determined for both cell lines. The expression levels of neurogenic cell markers were compared consecutively. With respect to the surface marker profile, both cells display similar pluripotency phenotypes. Both cells successfully differentiated into osteo-and adipogenic cell lines. The immune staining of mesenchymal, stem cell and neurogenic markers gave positive reaction. The gene expression level for Tubb3, Nestin, Gfap, Map2, Nf-h, and Nf-l was higher in hBT-SCs than hBM-MSCs. The high level of neurotrophic factors, like Tenascin C, NGF, BDNF, VEGF, and CNTF might indicate their regeneration and maintenance capacity in damaged neural tissue. Besides they are alternative source for human mesenchymal stem cells, hBT-SCs assess the possibility to use in clinical studies. ß
Therefore, we are introducing a novel type of stem cell with immunomodulatory properties. On the other hand, it is questionable why PI-SCs cannot protect the insulin producing cells from attacks of autoreactive T-cells in the developing of type1 diabetes. For this purpose, further molecular researches in vitro and in vivo are needed to clarify why PI-SCs may not suppress attacks of autoreactive-immune-cells towards PIs. PI-SCs from diseased people should be compared with pancreas of healthy ones at both genomic and proteomic levels.
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