iPSC- and mesenchymoangioblast-derived mesenchymal stem cells provide greater protection against experimental chronic allergic airways disease compared with a clinically used corticosteroid.

The airway remodeling (AWR) associated with chronic allergic airways disease (AAD)/asthma contributes to irreversible airway obstruction. This study compared and combined the antiremodeling and other effects of induced pluripotent stem cell and mesenchymoangioblast-derived mesenchymal stem cells (MCA-MSCs) with the corticosteroid dexamethasone (Dex) in experimental chronic AAD/asthma. Female BALB/c mice subjected to 11 wk of ovalbumin (Ova)-induced chronic AAD were intranasally administered MCA-MSCs (1 × 106 cells/mouse; once weekly on wk 10 and 11), Dex (0.5 mg/ml; once daily for 2 wk), or both combined. MCA-MSC detection and changes in airway inflammation (AI), AWR, and airway hyperresponsiveness (AHR) were measured at the end of wk 11. Mice with chronic AAD had significant AI, goblet cell metaplasia, epithelial damage/thickening, aberrant TGF-ß1 levels, subepithelial myofibroblast accumulation, airway/lung fibrosis, and AHR (all P < 0.001 vs. healthy controls). MCA-MSCs were detected in the lungs up to 5-7 d postadministration and demonstrated modest anti-inflammatory but striking antifibrotic effects against Ova-induced AAD, effectively decreasing AHR by 70-75% (all P < 0.05 vs. Ova alone). In comparison, Dex predominantly demonstrated anti-inflammatory effects, decreasing AHR by ∼30%. Combining MCA-MSCs with Dex provided equivalent protection to that offered by either therapy alone. MCA-MSCs reduce chronic AAD-induced AWR and AHR to a greater extent than Dex and may act as a suitable adjunct therapy to corticosteroid treatment of asthma.-Royce, S. G., Mao, W., Lim, R., Kelly, K., Samuel, C. S. iPSC- and mesenchymoangioblast-derived mesenchymal stem cells provide greater protection against experimental chronic allergic airways disease compared with a clinically used corticosteroid.

Hydro-climatic changes and their impacts on vegetation in Xinjiang, Central Asia.

Central Asia is one of the most arid regions in the world. Xinjiang is the core area of the arid region in Central Asia. Climate warming and hydrological changes might affect the vegetation dynamics in the region; however there has been no systematic evaluation of the hydro-climatic changes and their impacts on vegetation in Xinjiang. In this study, the vegetation growth and its response to hydro-climatic changes from 2003 to 2013 were analyzed based on multiple satellite observations. It was found that precipitation increased, with fluctuations, at a rate of 12.07 mm/decade, and evapotranspiration decreased, also with fluctuations, at a rate of -14.79 mm/decade. The change in total water storage, derived from the Gravity Recovery and Climate Experiment satellite, displayed an increasing trend, with a rate of increase of 112.91 mm/decade. The changes in the Global Land Data Assimilation System-derived soil moisture and groundwater estimated by the water budget presented a slight increasing trend from 2003 to 2013. The total water storage, soil moisture, and groundwater all significantly increased after 2008, and the increases in soil moisture and groundwater had positive effects on the increasing total water storage in Xinjiang. There were more obvious time lags in the response of changes in total water storage to precipitation than for the changes in soil moisture. The changes in the normalized difference vegetation index from 2003 to 2013 indicated a slight greening, and the accumulated normalized difference vegetation index anomalies also increased sharply after 2008. There were significant increases in the Tianshan Mountains, Altay Mountains, and around the Tarim Basin, especially along the Tarim River. The results suggested that the changes in total water storage and soil moisture were regarded as better indicators of the vegetation dynamics than other hydro-climatic variables in Xinjiang. Climate warming has led to accelerated glacier shrinkage and snow melt, and the increased runoff is likely to lead to more infiltration of surface water into the soil and ground, resulting in increased total water storage.

Serelaxin enhances the therapeutic effects of human amnion epithelial cell-derived exosomes in experimental models of lung disease.

BACKGROUND AND PURPOSE: There is growing interest in stem cell-derived exosomes for their therapeutic and regenerative benefits given their manufacturing and regulatory advantages over cell-based therapies. As existing fibrosis impedes the viability and efficacy of stem cell/exosome-based strategies for treating chronic diseases, here we tested the effects of the anti-fibrotic drug, serelaxin, on the therapeutic efficacy of human amnion epithelial cell (AEC)-derived exosomes in experimental lung disease. EXPERIMENTAL APPROACH: Female Balb/c mice were subjected to either the 9.5-week model of ovalbumin and naphthalene (OVA/NA)-induced chronic allergic airway disease (AAD) or 3-week model of bleomycin (BLM)-induced pulmonary fibrosis; then administered increasing concentrations of AEC-exosomes (5 µg or 25µg), with or without serelaxin (0.5mg/kg/day) for 7-days. 1x106 AECs co-administered with serelaxin over the corresponding time-period were included for comparison in both models, as was pirfenidone-treatment of the BLM model. Control groups received saline/corn oil or saline, respectively. KEY RESULTS: Both experimental models presented with significant tissue inflammation, remodelling, fibrosis and airway/lung dysfunction at the time-points studied. While AEC-exosome (5 µg or 25µg)-administration alone demonstrated some benefits in each model, serelaxin was required for AEC-exosomes (25µg) to rapidly normalise chronic AAD-induced airway fibrosis and airway reactivity, and BLM-induced lung inflammation, epithelial damage and subepithelial/basement membrane fibrosis. Combining serelaxin with AEC-exosomes (25µg) also demonstrated broader protection compared to co-administration of serelaxin with 1x106 AECs or pirfenidone. CONCLUSIONS AND IMPLICATIONS: Serelaxin enhanced the therapeutic efficacy of AEC-exosomes in treating basement membrane-induced fibrosis and related airway dysfunction.