Stem cell-derived extracellular vesicles inhibit and revert fibrosis progression in a mouse model of diabetic nephropathy.

Abstract Extracellular vesicles (EVs) that are derived from mesenchymal stromal cells (MSCs) have been shown to reprogram injured cells by activating regenerative processes. We herein investigate the potential therapeutic effect of EVs, shed by human bone marrow MSCs and by human liver stem-like cells (HLSCs), on the progression and reversion of fibrosis in a mouse model of diabetic nephropathy, as induced by streptozotocin. After the development of nephropathy, stem cell-derived EVs were administered weekly to diabetic mice for four weeks. The stem cell-derived EV treatment, but not the fibroblast EV treatment that was used as a control, significantly ameliorated functional parameters, such as albumin/creatinine excretion, plasma creatinine and blood urea nitrogen, which are altered in diabetic mice. Moreover, the renal fibrosis that develops during diabetic nephropathy progression was significantly inhibited in stem cell EV-treated animals. A correlation was found between the down regulation of several pro-fibrotic genes in renal tissues and the anti-fibrotic effect of HLSC and MSC EVs. A comparative analysis of HLSC and MSC EV miRNA content highlighted some common and some specific patterns of miRNAs that target predicted pro-fibrotic genes. In conclusion, stem cell-derived EVs inhibit fibrosis and prevent its progression in a model of diabetes-induced chronic kidney injury

PDGF enhances the protective effect of adipose stem cell-derived extracellular vesicles in a model of acute hindlimb ischemia

Abstract We previously have shown that platelet-derived growth factor (PDGF) modulates the biological activity of extracellular vesicles released by adipose-derived mesenchymal stem cells (ASC-EVs). ASC-EVs may interact with blood and vessel cells by transferring proteins and nucleic acids and regulate their functions. In this study, we investigated immunomodulatory activity and protection from acute hindlimb ischemia of EVs released by PDGF-stimulated ASC (PDGF-EVs). PDGF treatment of ASC changed protein and RNA composition of released EVs by enhancing the expression of anti-inflammatory and immunomodulatory factors. In vitro, control EVs (cEVs) derived from non-stimulated ASC increased the secretion of both the IL-1b, IL-17, IFNγ, TNFα pro-inflammatory factors and the IL-10 anti-inflammatory factor, and enhanced the in vitro peripheral blood mononuclear cell (PBMC) adhesion on endothelium. In contrast, PDGF-EVs enhanced IL-10 secretion and induced TGF-β1 secretion by PBMC. Moreover, PDGF-EVs stimulated the formation of T regulatory cells. In vivo, PDGF-EVs protected muscle tissue from acute ischemia, reduced infiltration of inflammatory cells and increased T regulatory cell infiltration in respect to cEVs. Our results suggest that PDGF-EVs are enriched in anti-inflammatory and immunomodulatory factors and induced in PBMC an enhanced production of IL-10 and TGF-β1 resulting in protection of muscle from acute ischemia in vivo

Chlorate as disinfection by-product in Turin drinking water treatment plant: formation, monitoring, solution possibilities

Chlorine dioxide application in drinking water disinfection avoids trihalomethanes, but it can generate other disinfection by-products (DBPs): chlorite and chlorate. This paper concerns chlorate ion formation during chlorine dioxide generation and oxidation reactions, in relation with the use of sodium hypochlorite solutions. This aspect is very important taking into account that current WHO Drinking water Guidelines suggest a limit of 700 µg/L for chlorate ion. SMAT (the drinking water supplier of the town of Turin, northern Italy) uses both chlorine dioxide and sodium hypochlorite in its three surface water treatment plants, having a whole potentiality of about 40 M m3/y. This research considered the following issues: chlorate neo-formation processes, potential precursors and influencing conditions, and process and plant minimization intervents. The three treatment lines were analyzed by monitoring for nine months chlorate concentration in significant phases of the potabilization process and in the outflow, in order to detect the most critical conditions. Chlorate formation can be bound both to the natural degradation of hypochlorite, and to different dismutation phenomena occurring during disinfection. The first contribution can be more easily controlled: a refrigerated storage of hypochlorite was evaluated on laboratory and pilot scale, and taking into account its effectiveness to comply with WHO guidelines, this improvement will be shortly adopted in full scal

Chlorate as disinfection by-product in Turin drinking water treatment plant: formation, monitoring, solution possibilities

Chlorine dioxide application in drinking water disinfection avoids trihalomethanes, but it can generate other disinfection by-products (DBPs): chlorite and chlorate. This paper concerns chlorate ion formation during chlorine dioxide generation and oxidation reactions, in relation with the use of sodium hypochlorite solutions. This aspect is very important taking into account that current WHO Drinking water Guidelines suggest a limit of 700 µg/L for chlorate ion. SMAT (the drinking water supplier of the town of Turin, northern Italy) uses both chlorine dioxide and sodium hypochlorite in its three surface water treatment plants, having a whole potentiality of about 40 M m3/y. This research considered the following issues: chlorate neo-formation processes, potential precursors and influencing conditions, and process and plant minimization intervents. The three treatment lines were analyzed by monitoring for nine months chlorate concentration in significant phases of the potabilization process and in the outflow, in order to detect the most critical conditions. Chlorate formation can be bound both to the natural degradation of hypochlorite, and to different dismutation phenomena occurring during disinfection. The first contribution can be more easily controlled: a refrigerated storage of hypochlorite was evaluated on laboratory and pilot scale, and taking into account its effectiveness to comply with WHO guidelines, this improvement will be shortly adopted in full scale