Comparative Analyses of Immunosuppressive Characteristics of Bone-Marrow, Wharton's Jelly, and Adipose Tissue-Derived Human Mesenchymal Stem Cells.

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 ß1, 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.

Appetite-regulating hormones in chronic kidney disease patients.

OBJECTIVE: Inflammation and loss of appetite is the most common problem in patients with chronic kidney disease (CKD). This comparative cross-sectional study aimed to characterize the changes in circulating levels of ghrelin, obestatin, leptin, all of which have an effect on food intake, and proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) in patients with CKD who were undergoing different treatments. DESIGN AND SETTING: Study participants included 36 patients who had undergone hemodialysis (body mass index [BMI]: 22.3 ± 4.17 kg/m(2)); 41 who had undergone peritoneal dialysis (BMI: 23.5 ± 3.10 kg/m(2)), 30 with early stage CKD (BMI: 24.4 ± 3.32 kg/m(2)), and 31 healthy subjects (24.3 ± 2.14 kg/m(2)). The patients with CKD were kept under a standard diet with restricted salt, potassium, and protein intake. INTERVENTION: Levels of leptin, acylated ghrelin, obestatin, TNF-α, and IL-6 were measured by commercially available enzyme-linked immunosorbent assay kits. Total nitrite/nitrate was analyzed using colorimetric assay kit. RESULTS: Significantly high leptin levels, accompanied by low acylated ghrelin levels, were observed in patients with CKD. Maintenance dialysis did not affect these levels. TNF-α and IL-6 levels were significantly higher in CKD patients than in healthy subjects, the highest being in dialysis patients. Obestatin levels were relatively low in patients who had undergone hemodialysis. CONCLUSION: Low acyl-ghrelin levels, accompanied with high levels of TNF-α and IL-6 may be involved in the loss of appetite and poor nutritional status in CKD patients.

Adiponectin is a link among inflammation, insulin resistance, and high-density lipoprotein cholesterol but is not associated with paraoxonase activity in premenopausal women.

The aim of this study was to evaluate whether insulin sensitivity, inflammatory response, and plasma lipid profile are associated with circulating adiponectin levels in nondiabetic healthy women. The authors also assessed whether adiponectin has any effect on high-density lipoprotein cholesterol-linked paraoxonase 1 (PON-1) activity and on the susceptibility of low-density lipoproteins to oxidation. Plasma adiponectin was measured in 91 nondiabetic premenopausal women, and the patients were then divided into quartiles. Circulating adiponectin was found to be associated with body mass index (r=.55, P<.001). After adjustment for body mass index, adiponectin showed an inverse correlation with the homeostasis model assessment of insulin resistance (HOMA-IR) (r=-.41, P<.001) and a positive correlation with high-density lipoprotein cholesterol (r=.43, P<.001). In linear regression analysis, HOMA-IR, tumor necrosis factor alpha, and high-density lipoprotein cholesterol levels were found to be independently associated with adiponectin. However, high-density lipoprotein cholesterol-linked PON-1 activity and the susceptibility of low-density lipoproteins to in vitro oxidation did not seem to be related to plasma adiponectin concentrations.

Dimethylarginines and inflammation markers in patients with chronic kidney disease undergoing dialysis.

The aim of this study was to investigate the pro-oxidant and proinflammatory biomarkers and their relationship with dimethylarginines (DMAs) in patients at various stages of chronic kidney disease (CKD). We studied 114 CKD patients, 36 were hemodialyzed, 41 peritoneal dialyzed and 37 nondialyzed (early stage) CKD patients. The control group consisted of 31 healthy subjects. Plasma levels of asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), L-arginine, nitric oxide (NO) and proinflammatory cytokines (TNF-alpha and IL-6) were determined, and their relationships with the degree of disease were evaluated. Both DMAs were at high levels in all CKD patients, whereas arginine concentrations were low in patients undergoing dialysis. Elevated TNF-alpha and IL-6 in CKD patients were indicative of ongoing chronic inflammatory state. A significant positive correlation between SDMA and creatinine suggests that plasma SDMA level may be an index for renal function.