No abstract

Previous studies have revealed that mesenchymal stem cells (MSCs) alleviate inflammatory bowel disease (IBD) by modulating inflammatory cytokines in the inflamed intestine. However, the mechanisms underlying these effects are not completely understood. We sought to investigate the therapeutic effects of human adipose tissue-derived (hAT)-MSCs in an IBD mouse model and to explore the mechanisms of the regulation of inflammation. Dextran sulfate sodium-induced colitis mice were infused with hAT-MSCs intraperitoneally and colon tissues were collected on day 10. hAT-MSCs were shown to induce the expression of M2 macrophage markers and to regulate the expression of pro- and anti-inflammatory cytokines in the colon. Quantitative real time-PCR analyses demonstrated that less than 20 hAT-MSCs, 0.001% of all intraperitoneally injected hAT-MSCs, were detected in the inflamed colon. To investigate the effects of hAT-MSC-secreted factors in vitro, transwell co-culture system was used, demonstrating that tumour necrosis factor-α-induced gene/protein 6 (TSG-6) released by hAT-MSCs induces M2 macrophages. In vivo, hAT-MSCs transfected with TSG-6 small interfering RNA, administered intraperitoneally, were not able to induce M2 macrophage phenotype switch in the inflamed colon and had no significant effects on IBD severity. In conclusion, hAT-MSC-produced TSG-6 can ameliorate IBD by inducing M2 macrophage switch in mice.

Disturbances in emotional functioning are a major cause of persistent functional disability in schizophrenia. However, it is not clear what specific aspects of emotional functioning are impaired. Some studies have indicated diminished experience of positive affect in individuals with schizophrenia, while others have not. The current study assessed emotional responses by 34 individuals with schizophrenia and 35 demographically matched healthy participants to 131 images sampling a wide range of emotional arousal and valence levels. Ratings of affective response elicited by individual images were highly correlated across the groups (r's>.90), indicating similar emotional experiences at the moment of stimulus exposure. However, the data did not indicate strong relationships between ratings of the emotional impact of the images and most measures of day-to-day emotional processing. These results demonstrate that individuals with schizophrenia report "normal" emotional responses to emotional stimuli, and thus suggests that deficits in emotional functioning associated with the disorder are likely to occur further downstream, and involve the effective integration of emotion and cognition for adaptive functioning in areas such as goal-setting, motivation, and memory.

Silver (or platinum)-containing calcium phosphate (hydroxyapatite (HA) and tricalcium phosphate (alpha-TCP)) coatings on titanium substrates were formed by micro-arc oxidation (MAO) and their in vitro antibacterial activity and in vitro cytotoxicity were evaluated. MAO was performed in an electrolytic solution containing beta-glycerophosphate disodium salt pentahydrate (beta-GP) and calcium acetate monohydrate (CA), and Ag and Pt were introduced in the form of AgNO(3) (or CH(3)COOAg) and H(2)PtCl(6), respectively. The MG63 and human osteosarcoma (HOS) cell lines were used to investigate the proliferation and differentiation behavior of the cells, respectively, whereas two strains of bacteria, Staphylococcus aureus and Escherichia coli, were used to evaluate the antibacterial activity of the coatings. The phase, morphology, and Ag content of the coatings were strongly dependent on the applied voltage and Ag precursor concentration. HA and alpha-TCP phases were detected in the coatings oxidized above 400 V and the presence of Ag was confirmed by EDS. While the coatings with a high content of Ag were cytotoxic and those obtained in the Pt-containing electrolyte had no apparent antibacterial activity, the calcium phosphate coatings obtained in the low Ag concentration electrolyte exhibited in vitro antibacterial activity but no cytotoxicity. Thus, biocompatible calcium phosphate coatings on Ti implants with antibacterial activity can be achieved by one-step MAO.

The inflammatory bowel diseases (IBD) are characterized by relapsing inflammation and immune activation diseases of the gastrointestinal tract. Extracellular vesicles, which elicit similar biological activity to the stem cell themselves, have been used experimentally to treat dextran sulfate sodium (DSS)-induced colitis in murine models though immunosuppressive potential. In this study, we investigated whether the Extracellular vesicles (EVs) obtained by stimulating inflammatory cytokine on canine adipose mesenchymal stem cells (cASC) improved anti-inflammatory and/or immunosuppressive potential of EVs, and/or their ability to alleviate inflammation in colitis. We also explored the correlation between immune cells and the inflammatory repressive effect of primed EVs. Pro-inflammatory cytokines such as TNF-α and ifn-γ increased immunosuppressive protein such as HGF, TSG-6, PGE2 and tGf-β in EVs. Moreover, the anti-inflammatory effect of EVs was improved through pretreatment with inflammatory cytokines. Importantly, EVs obtained from primed stem cells effectively induced macrophage polarization toward an anti-inflammatory M2 phenotype and suppressed activated immunity by enhancing regulatory T cells in inflamed colon in mice. Our results provide a new and effective therapy for the EVs obtained from ASC stimulated with TNF-α and ifn-γ against not only iBD, but also immune-mediated disease.