Background Chronic obstructive pulmonary disease (COPD) is an incurable and debilitating chronic disease characterized by progressive airflow limitation associated with abnormal levels of tissue inflammation. Therefore, stem cell-based approaches to tackle the condition are currently a focus of regenerative therapies for COPD. Extracellular vesicles (EVs) released by all cell types are crucially involved in paracrine, extracellular communication. Recent advances in the field suggest that stem cell-derived EVs possess a therapeutic potential which is comparable to the cells of their origin. Methods In this study, we assessed the potential anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSC)-derived EVs in a rat model of COPD. EVs were isolated from hUC-MSCs and characterized by the transmission electron microscope, western blotting, and nanoparticle tracking analysis. As a model of COPD, male Sprague-Dawley rats were exposed to cigarette smoke for up to 12 weeks, followed by transplantation of hUC-MSCs or application of hUC-MSC-derived EVs. Lung tissue was subjected to histological analysis using haematoxylin and eosin staining, Alcian blue-periodic acid-Schiff (AB-PAS) staining, and immunofluorescence staining. Gene expression in the lung tissue was assessed using microarray analysis. Statistical analyses were performed using GraphPad Prism 7 version 7.0 (GraphPad Software, USA). Student’s t test was used to compare between 2 groups. Comparison among more than 2 groups was done using one-way analysis of variance (ANOVA). Data presented as median ± standard deviation (SD). Results Both transplantation of hUC-MSCs and application of EVs resulted in a reduction of peribronchial and perivascular inflammation, alveolar septal thickening associated with mononuclear inflammation, and a decreased number of goblet cells. Moreover, hUC-MSCs and EVs ameliorated the loss of alveolar septa in the emphysematous lung of COPD rats and reduced the levels of NF-κB subunit p65 in the tissue. Subsequent microarray analysis revealed that both hUC-MSCs and EVs significantly regulate multiple pathways known to be associated with COPD. Conclusions In conclusion, we show that hUC-MSC-derived EVs effectively ameliorate by COPD-induced inflammation. Thus, EVs could serve as a new cell-free-based therapy for the treatment of COPD.

The present study is aimed at optimizing the in vitro culture protocol for generation of rat bone marrow- (BM-) derived mesenchymal stem cells (MSCs) and characterizing the culture-mediated cellular senescence. The initial phase of generation and characterization was conducted using the adherent cells from Sprague Dawley (SD) rat's BM via morphological analysis, growth kinetics, colony forming unit capacity, immunophenotyping, and mesodermal lineage differentiation. Mesenchymal stem cells were successfully generated and characterized as delineated by the expressions of CD90.1, CD44H, CD29, and CD71 and lack of CD11b/c and CD45 markers. Upon induction, rBM-MSCs differentiated into osteocytes and adipocytes and expressed osteocytes and adipocytes genes. However, a decline in cell growth was observed at passage 4 onwards and it was further deciphered through apoptosis, cell cycle, and senescence assays. Despite the enhanced cell viability at later passages (P4-5), the expression of senescence marker, β-galactosidase, was significantly increased at passage 5. Furthermore, the cell cycle analysis has confirmed the in vitro culture-mediated cellular senescence where cells were arrested at the G0/G1 phase of cell cycle. Although the currently optimized protocols had successfully yielded rBM-MSCs, the culture-mediated cellular senescence limits the growth of rBM-MSCs and its potential use in rat-based MSC research.

The respiratory burst activity of neutrophils could be affected by DM and the elevation of ROS production might be an aggravating factor in diabetic-related complications.

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Chronic obstructive pulmonary disease (COPD) is characterized by irreversible loss of lung function that stem from two mechanisms, inflammation and senescence. Crosstalk between these two mechanisms accelerate the development of COPD, thus targeting these two pathways may offer benefits in the treatment of COPD. Growing amount of evidence have shown that mesenchymal stem cells as a promising candidate for the treatment of COPD.Over the years, many studies conducted to decipher the therapeutic effect of MSC in COPD and the mechanisms involve, in the hope of utilizing these cells as new therapeutic strategy for COPD. However, the cell-based therapy by using the MSC presented with many obstacles including low engraftment at the site of injury, the risk of microvascular occlusion, unwanted differentiation, and also the risk of malignant transformation. Recently, recently researchers begin to look at the possibility of using MSC derived extracellular vesicles as an alternative to MSC. Here we review the effect of MSC and MSC derived EV in modulating inflammation, and senescence in COPD. We also review current treatment and the side effect in COPD, and senolytic drugs, a new therapeutic strategy targeting the senescent cells. Chronic Obstructive Pulmonary DiseaseChronic obstructive pulmonary disease (COPD) has a tremendous economic impact on healthcare and is associated with high morbidity, and high mortality rate. Global Initiative for Chronic Obstructive Lung Disease (GOLD) in 2017 reported that more than 3 million people died in 2012 accounting for 6% of total death globally. It is estimated that the prevalence and the burden of COPD to increase in the coming decade and by 2020, COPD will become the third leading cause of death worldwide. Symptoms of COPD include chronic cough, dyspnea and excessive production of sputum, while anorexia, fatigue and weight loss may present in patient with severe COPD. The diagnosis of post-bronchodilator forced expiratory volume in one second (FEV1)/ forced vital capacity (FVC) ≤0.7 confirms the presence of airflow limitation. The body mass index (BMI) are also useful in predicting outcomes such as survival with the values <21 kg . m -2 are associated with increased mortality (Celli et al., 2004).Cigarette smoke is the main risk factor of COPD which accounts for 80-90% of all cases.However, environmental pollution, noxious gases, genetic predisposition, pulmonary infections, and aging can also increase the risk of COPD (Churg et el.,2008).