Allogeneic umbilical cord-derived mesenchymal stem cell transplantation for treating chronic obstructive pulmonary disease: a pilot clinical study.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. COPD results from chronic inflammation of the lungs. Current treatments, including physical and chemical therapies, provide limited results. Stem cells, particularly mesenchymal stem cells (MSCs), are used to treat COPD. Here, we evaluated the safety and efficacy of umbilical cord-derived (UC)-MSCs for treating COPD. METHODS: Twenty patients were enrolled, 9 at stage C and 11 at stage D per the Global Initiative for Obstructive Lung Disease (GOLD) classification. Patients were infused with 106 cells/kg of expanded allogeneic UC-MSCs. All patients were followed for 6 months after the first infusion. The treatment end-point included a comprehensive safety evaluation, pulmonary function testing (PFT), and quality-of-life indicators including questionnaires, the 6-min walk test (6MWT), and systemic inflammation assessments. All patients completed the full infusion and 6-month follow-up. RESULTS: No infusion-related toxicities, deaths, or severe adverse events occurred that were deemed related to UC-MSC administration. The UC-MSC-transplanted patients showed a significantly reduced Modified Medical Research Council score, COPD assessment test, and number of exacerbations. However, the forced expiratory volume in 1 s, C-reactive protein, and 6MWT values were nonsignificantly reduced after treatment (1, 3, and 6 months) compared with those before the treatment. CONCLUSION: Systemic UC-MSC administration appears to be safe in patients with moderate-to-severe COPD, can significantly improve their quality of life, and provides a basis for subsequent cell therapy investigations. TRIAL REGISTRATION: ISRCTN, ISRCTN70443938. Registered 06 July 2019.

Evaluation of physicochemical and hydromechanical properties of MSWI bottom ash for road construction.

Municipal Solid Waste Incinerator (MSWI) Bottom Ash has been used as a substitute for traditional aggregates in road construction; however, this material is little understood. The work presented in this paper pursues the study on the mechanical performance of bottom ash, proven by Le et al. (2017). Using a coupling technique for the first time, the physicochemical aspects and hydromechanical resistance of bottom ash were evaluated and analyzed. Physicochemical tests were first carried out, followed by oedometer tests under a wetting path. This coupled evaluation underlined the role of principal mineralogical components of the studied bottom ash as well as the link with its hydromechanical properties. Tests results showed that the principal constituent of bottom ash is SiO2, which thus affects the characteristics of bottom ash. Given the physical stability of SiO2 which generated a compacted material being less sensitive to water and chemical reactions, and bottom ash's other characteristics, this demonstrates why bottom ash could be a viable material in roadworks.

Elevation of fibrinogen due to loss of ovarian function enhances actin ring formation and leads to increased bone resorption.

The aim of the present study was to evaluate the effect of fibrinogen on number and function of osteoclasts (OC) consequently resulting in bone loss. It was hypothesized that the enhanced level of released fibrinogen due to loss of ovarian function caused bone loss by acting on OCs. Bone loss was induced by ovariectomy (OVX) in mice and analyzed by micro-CT. The effect of fibrinogen on OCs was evaluated by tartrate-resistant acid phosphatase, annexin V, actin staining, pit formation observed on dentine slices, and Western blotting. Exogenous fibrinogen increased OC survival, actin ring formation, and bone resorption in vitro. The effect of fibrinogen was dependent on ß(3)-integrin, which is a marker for mature OCs. Fibrinogen induced the activation of transforming oncogene from Ak strain (Akt), Ras-related C3 botulinum toxin substrate 1 (Rac1), and Rho family of GTPase (Rho) and the degradation of the Bcl-2 interacting mediator of cell death (Bim) in a manner similar to macrophage colony-stimulating factor (M-CSF). OVX increased plasma fibrinogen and serum M-CSF together with elevated actin ring formation and bone loss. The increased fibrinogen level due to loss of ovarian function may contribute, at least partly, to bone loss through the enhanced number and activity of OCs.