Bone marrow Mesenchymal Stem Cells (BM-MSCs), due to their strong protective and anti-inflammatory abilities, have been widely investigated in the context of several diseases for their possible therapeutic role, based on the release of a highly proactive secretome composed of soluble factors and Extracellular Vesicles (EVs). BM-MSC-EVs, in particular, convey many of the beneficial features of parental cells, including direct and indirect β-amyloid degrading-activities, immunoregulatory and neurotrophic abilities. Therefore, EVs represent an extremely attractive tool for therapeutic purposes in neurodegenerative diseases, including Alzheimer’s disease (AD). We examined the therapeutic potential of BM-MSC-EVs injected intracerebrally into the neocortex of APPswe/PS1dE9 AD mice at 3 and 5 months of age, a time window in which the cognitive behavioral phenotype is not yet detectable or has just started to appear. We demonstrate that BM-MSC-EVs are effective at reducing the Aβ plaque burden and the amount of dystrophic neurites in both the cortex and hippocampus. The presence of Neprilysin on BM-MSC-EVs, opens the possibility of a direct β-amyloid degrading action. Our results indicate a potential role for BM-MSC-EVs already in the early stages of AD, suggesting the possibility of intervening before overt clinical manifestations.

Greater Cairo (Egypt) is a megalopolis where the studies of the air pollution events are of extremely high relevance, for the geographical-climatological aspects, the anthropogenic emissions and the health impact. While preliminary studies on the particulate matter (PM) chemical composition in Greater Cairo have been performed, no data are yet available on the PM’s toxicity. In this work, the in vitro toxicity of the fine PM (PM_2.5) sampled in an urban area of Greater Cairo during 2017–2018 was studied. The PM_2.5 samples collected during spring, summer, autumn and winter were preliminary characterized to determine the concentrations of ionic species, elements and organic PM (Polycyclic Aromatic Hydrocarbons, PAHs). After particle extraction from filters, the cytotoxic and pro-inflammatory effects were evaluated in human lung A549 cells. The results showed that particles collected during the colder seasons mainly induced the xenobiotic metabolizing system and the consequent antioxidant and pro-inflammatory cytokine release responses. Biological events positively correlated to PAHs and metals representative of a combustion-derived pollution. PM_2.5 from the warmer seasons displayed a direct effect on cell cycle progression, suggesting possible genotoxic effects. In conclusion, a correlation between the biological effects and PM_2.5 physico-chemical properties in the area of study might be useful for planning future strategies aiming to improve air quality and lower health hazards.

Airborne particulate matter (PM) is the primary environmental cause of death worldwide. The understanding of the toxicological mechanism has improved over the last decades, nonetheless now novel exposure systems allow the possibility to mimic the in vivo interaction between particles or particle constituents and lung cells. Here we report the results obtained after exposure to the organic extract of fine PM (PM_2.5-0.3) of the BEAS-2B cells cultured in submerged or at the air liquid interface (ALI) conditions. Deposition efficiency of both PM and its organic extract was followed. Cell viability, inflammatory responses and gene expression were then evaluated. The comparison of submerged vs ALI exposure revealed significant differences in the expression of specific genes such as CYP1A1 and NQO1 6h after exposure and CYP1B1 and NFkB1 24h post exposure. Also, the results demonstrate the importance of evaluating the efficiency of deposition of the treatment to avoid misinterpretation of the results. PM particles determined an extremely low deposition efficiency, making it impossible to use this particle for ALI exposure tests. Although biological results, such as gene expression, may vary between the two exposure approaches (submerged or ALI), the ALI exposure should be preferred as it is more representative of human exposure via the respiratory route.