Abstract
The effects of adipose derived stromal cells (ASCs) were evaluated on tracheal responsiveness and biochemical parameters in guinea pigs model of chronic obstructive pulmonary disease (COPD). Thirty six guinea pigs were divided into 6 groups including: Control, COPD, COPD+intratracheal delivery of PBS (COPD+ITPBS), COPD+intravenous delivery of PBS (COPD+IVPBS), COPD+intratracheal delivery of ASCs (COPD+ITASC) and COPD+intravenous injection of ASCs (COPD+IVASC). COPD was induced by exposing animals to cigarette smoke for 3 months. Cell therapy was then performed and after 14 days, tracheal responsiveness, concentration of interleukin-8 (IL-8) in serum and broncho-alveolar lavage fluid (BALF), as well as total and differential white blood cells (WBC) counts were evaluated. Tracheal responsiveness, total WBC counts, neutrophil and eosinophil percentage in BALF as well as concentration of IL-8 in serum and BALF significantly increased but lymphocyte percentage decreased in COPD compared to the control group (P<0.05 to p<0.001). Cell therapy was able to restore the tracheal hyper-responsiveness and the increased IL-8 concentration in serum and BALF of COPD-ITASC but not COPD-IVASC animals (P<0.05 for all cases). Total WBC in BALF also showed a significant decrease in both treated groups and the percentages of eosinophils, neutrophils and lymphocytes in BALF were reversed in COPD-ITASC compared to COPD-ITPBS animals (P<0.05 to P<0.001). Therefore, intratracheal cell therapy with ASC can decrease tracheal hyperresponsiveness and lung inflammation in cigarette smoke induced-COPD which may be helpful in attenuation of the severity of disease in patients suffering from COPD.
Highlights
Chronic obstructive pulmonary disease (COPD) is expanding as the fourth leading cause of death in the world [1]
Adipose derived stromal cells (ASCs) and mesenchymal stem cells (MSCs) derived from ASCs are reported to have some beneficial action on pulmonary diseases [8,9,10,11]
Intratracheal administration of MSCs reduces the destruction in elastase-induced emphysema through secretion of paracrine factors such as epidermal growth factor [10]
Summary
Chronic obstructive pulmonary disease (COPD) is expanding as the fourth leading cause of death in the world [1]. Chronic obstructive bronchiolitis, increased airway responsiveness and emphysematous destruction of the lung parenchyma are the most usual pathologic changes observed in this progressive lung disease [2,3,4]. These changes are mostly due to repetitive exposure to cigarette smoke which induces inflammatory responses, oxidative stress and protease-antiprotease imbalance in the lung [4,5,6]. Gupta et al, showed that beneficial effect of bone marrow-derived MSCs on endotoxin-induced lung injury is independent of their ability to engraft in the lung and is related to down-regulation of proinflammatory responses to endotoxin (e.g. reducing TNFalpha in the bronchoalveolar lavage and plasma) and increasing anti-inflammatory cytokines (e.g. IL-10) [12]
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