Adipose-Derived Stromal Cell Therapy Affects Lung Inflammation and Tracheal Responsiveness in Guinea Pig Model of COPD

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.

Experimental animal models for COPD: a methodological review

“…Total WBC, eosinophils and neutrophils in lung lavage of COPD guinea pigs were also increased [52]. In Table 3, a summary of total and differential WBC in the blood and lung lavage in different animal models of COPD was presented.…”

“…In addition, Feizpour et al indicated that the level of IL-8 in serum and BAL of guinea pig models of CS-induced COPD, were increased [52]. Inflammatory mediators and cytokines changes in the blood and lung lavage in different animal models of COPD were presented in Table 3.…”

Fibroblast Growth Factor 1-Transfected Adipose-Derived Mesenchymal Stem Cells Promote Angiogenic Proliferation

“…The AD-MSCs at passage 3 were seeded into 12-well plates at a density of 1 • 10 4 cells per well and cultured for 24 h in DMEM containing antibiotics and 10% FBS, and were then incubated with a differentiation medium consisting of DMEM supplemented with antibiotics, 3% FBS, 250 mM IBMX (Fluka, Switzerland), 1 mM dexamethasone, 5 mM indomethacin, 0.2 mM insulin, 34mM D-pantothenate, and 66 mM biotin. The cells were maintained in this medium for 3 days and then cultured in an adipogenic maintenance medium consisting of DMEM supplemented with 3% FBS, 0.2 mM insulin, 1 mM dexamethasone, 34 mM D-pantothenate, and 66 mM biotin for 9 days (Yu et al, 2011;Feizpour et al, 2014). Adipogenesis was evaluated using the Oil-Red O staining method and photographed (Aguena et al, 2012).…”

Effects of Streptozotocin-Induced Diabetes on Proliferation and Differentiation Abilities of Mesenchymal Stem Cells Derived from Subcutaneous and Visceral Adipose Tissues

“…Then, the cells were incubated with the differentiation medium consisting of DMEM supplemented with antibiotic, 3 % FBS, 250 µM IBMX, 5 µM indomethacin, 0.2 µM insulin, 1 µM dexamethasone, 34 µM d-panthothenate, and 66 µM biotin. The cells were maintained in this medium for 3 days and then cultured for 9 days in adipocyte maintenance medium consisting of DMEM supplemented with 3 % FBS, 0.2 µM insulin, 1 µM dexamethasone, 34 µM d-panthothenate, and 66 µM biotin [18,19]. The level of adipogenesis was evaluated by Oil Red O staining [20,21].…”