Effects of 15-lipoxygenase overexpressing adipose tissue mesenchymal stem cells on the Th17/Treg plasticity

15-lipoxygenase (15-LOX) is a critical enzyme that allows the direction of arachidonic acid metabolism to change from inflammation into the resolution. This study aims to reveal how the immunomodulation properties of mesenchymal stem cells (MSC) alter by the 15-LOX overexpression. For this purpose, peripheral blood mononuclear cells (PBMCs) isolated from seven healthy volunteers, and both MSCs and 15-LOX overexpressing MSCs (15-LOXMSCs) were co-cultured at different cell ratios (1/1, 1/5 and 1/10). Alterations of CD4+Tbet+, CD4+Gata3+, CD4+RoRC2+, and CD4+FoxP3+ lymphocyte frequencies were detected by flow cytometry, and IFN-gamma, IL-4, IL-6, IL-10, IL-17a, TGF-13 and LXA4 levels of medium supernatants were measured by ELISA method. According to our findings, MSC and 15-LOXMSCs have a suppressive effect on PHA activated PBMCs. However, as the ratio of PBMCs increased, the effects of 15-LOXMSCs increased significantly, while the effects of MSCs decreased. The most notable effect of the 15-LOX modification was the significant reduction in IL-6, IL-10 and IL17a expression and the accompanying increase in TGF-13 and LXA4 levels. We also observed a similar situation between CD4+RoRC2+ and CD4+FoxP3+ cell frequencies. These data suggested that the effects of MSCs on the balance of Th17 / Treg could change by the 15-LOX overexpression, and this might be in favor of the Treg cells.The Scientific Research Projects Commission of Ege University financially supported the project for this study, with the reference number 16-TIP-041.Scientific Research Projects Commission of Ege University [16-TIP-041

The Comparison of Second Trimester Screening Tests With the White Blood Cell Counts

WOS: 000387140800002Objective: Our aim was to determine the possible differences in the maternal immune system by comparing white blood cells (WBCs) count with the sub-parameters in pregnant women with high-risk and no-risk for seconder trimester screening. Materials and Methods: The results of complete blood count (CBC) and second trimester screening (STS) tests made between January 2011 and September 2015 of women meeting the inclusion criteria were analyzed retrospectively. All test results of pregnant women with high-risk for trisomy 21 (n = 55), neural tube defect (NTD) (n = 45) and with no-risk (n = 55) were compared. Trisomy 18 could not be evaluated due to limited number of cases. Results: The monocyte count (P < 0.001) of T21 group were significantly increased compared to control group, but neutrophil to lymphocyte ratio (N/L) (P = 0.027), lymphocyte to monocyte ratio (L/M) (P < 0.001) and neutrophil to monocyte ratio (N/M) (P < 0.001) were significantly decreased. The WBC (P = 0.02), monocyte (P < 0.001) and lymphocyte (P < 0.001) count of NTD group were significantly increased compared to control group, but N/L (P = 0.02), L/M (P = 0.034) and N/M ratio (P < 0.001) were decreased. Conclusion: The interaction of maternal immune system with the abnormal fetus may change the compositions of peripheral blood WBC and sub-parameters. Some of these changes may increase the predictive sensitivity of STS test. Further prospective studies are needed to confirm these findings

A comparison of cancer stem cell markers and nonclassical major histocompatibility complex antigens in colorectal tumor and noncancerous tissues

WOS: 000387934000012PubMed ID: 27806848Colorectal carcinoma (CRC) is one of the most fatal types of cancer in both women and men, and, unfortunately, patients are often diagnosed at an advanced stage. Cancer stem cells (CSCs) are associated with poor prognosis, metastasis, and recurrence, as well as chemotherapy and radiotherapy resistance. Therefore, different treatment alternatives are needed to facilitate the elimination of CSCs. One such approach is immunotherapy; however, tumor cells can evade immune cells by alteration of the expression patterns of human leukocyte antigens (HLA). In this study, we immunohistochemically investigated the expression patterns of CSC-specific markers CD44, CD133, Nanog, and Oct3/4, and immunosuppressive molecules HLA-G and -E in advanced CRC tumor tissues and noncancerous colon biopsies. We found significantly increased CD44, Nanog, Oct3/4, HLA-G, and HLA-E expression in the CRC tumor tissues compared with the noncancerous colon biopsies. These findings suggest that some tumor cells may be CSC-like and that the increased expression of HLA-G and HLA-E may be considered as an immune-evasive adaptation. Therefore, the nonclassical major histocompatibility complex class Ib antigens HLA-G and HLA-E may be potential targets in the elimination of CRC-CSCs. However, more detailed studies are required to support our findings. (C) 2016 Elsevier Inc. All rights reserved.Scientific Research Projects Commission of Celal Bayar UniversityCelal Bayar University [2014/166]The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The Scientific Research Projects Commission of Celal Bayar University supported the project for this study, whose reference number is 2014/166

Mesenchymal Stem Cells: a Potential Treatment Approach for Refractory Chronic Spontaneous Urticaria

Ozdemir, Alper Tunga/0000-0002-7708-077XWOS: 000581897300001PubMed: 33089453The etiopathogenesis of chronic spontaneous urticaria (CSU) is not fully elucidated, and almost 30-40% of patients are resistant to treatments; therefore, there is still a need for the development of new and effective treatments. This study aimed to develop experimental cellular therapy for CSU patients resistant to current treatment options. Autologous adipose tissue mesenchymal stem cells (MSC) were administered to 10 refractory CSU patients who were then followed up for six months. the efficacy of treatment was evaluated according to the weekly urticaria activity scores (UAS7) and drug use scores (DUS7). To observe the effect of treatment on immune cells, CD4(+) T cell subsets were analyzed by flow cytometry, and the serum IFN-gamma, TNF-alpha, IL2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17a, IL-21, IL-22, TGF-beta 1, PGE2, IDO and anti-Fc epsilon RI levels were measured using the Luminex and ELISA methods. the values obtained were compared with 10 control refractory CSU patients and five healthy controls. We found that the T cell subsets and inflammatory molecules were not affected by MSC treatment during the follow-up period. in control patients, a significant decrease was detected only at the Th2 subset, TGF-beta 1, PGE2, IDO and anti-Fc epsilon RI levels on the 14th day of treatment. the UAS7 and DUS7 values of the MSC-treated patients significantly decreased during the follow-up period, but in control patients, a significant but temporary decrease was seen. According to our findings, unlike conventional treatment, MSC therapy resulted in longer and more effective recovery. Our data indicate that MSCs may be an alternative and effective approach for treatment-resistant CSU patients.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [215 S 612]The Scientific and Technological Research Council of Turkey (TUBITAK) financially supported this study with reference number 215 S 612

The paracrine immunomodulatory interactions between the human dental pulp derived mesenchymal stem cells and CD4 T cell subsets

WOS: 000388823700011PubMed ID: 27576175Mesenchymal stem cells (MSCs) have strong immunomodulatory properties, however these properties may show some differences according to the tissue type of their isolate. In this study we investigated the paracrine interactions between human DP derived MSCs (hDP-MSCs) and the CD4(+) T helper cell subsets to establish their immunomodulatory mechanisms. We found that the CD4(+)-Tbet(+) (Th1) and CD4(+)-Gata3(+) (Th2) cells were suppressed by the hDP-MSCs, but the CD4(+)-Stat3(+) (Th17) and CD4(+)-CD25(+)-FoxP3(+) (Treg) cells were stimulated. The expressions of T cell specific cytokines interferon gamma (IFN-g), interleukin (IL)-4 and IL-17a decreased, but IL-10 and transforming growth factor beta-1 (TGF-b1) increased with the hDP-MSCs. The expressions of indoleamine-pyrrole 2,3-dioxygenase (IDO), prostaglandin E2 (PGE2), soluble human leukocyte antigen G (sHLA-G) derived from hDP-MSCs slightly increased, but hepatocyte growth factor (HGF) significantly increased in the co-culture groups. According to our findings, the hDP-MSCs can suppress the Th1 and Th2 subsets but stimulate the Th17 and Treg subsets. The Stat3 expression of Th17 cells may have been stimulated by the HGF, and thus the pro-inflammatory Th17 cells may have altered into the immunosuppressive regulatory Th17 cells. Further prospective studies are needed to confirm our findings. (C) 2016 Elsevier Inc. All rights reserved.Scientific Research Projects Commission of Celal Bayar UniversityCelal Bayar University [2013/136]The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The Scientific Research Projects Commission of Celal Bayar University supported the project for this study, whose reference number is 2013/136