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

<div><p>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 (<i>P</i><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 (<i>P</i><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 (<i>P</i><0.05 to <i>P</i><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.</p></div

Differentiation of adipose stromal cells to adipocyte and osteocyte lineage.

<p>The stromal cells were cultured in adipogenic or osteogenic differentiating media for 12 and 14 days, respectively. (A) Stromal cells cultured in control media; (B) Oil Red O staining of cultured cells in adipogenic differentiating media; (C) Alizarin Red staining of cells cultured in osteogenic differentiating media. Magnification ×100.</p

Effect of adipose derived stromal cells (ASCs) therapy on EC₅₀ methacholine (the effective concentration caused 50% of maximum contraction response to methacholine) in different groups of animals.

<p>Data are presented as mean ± SEM (big symbols with bars). The animals in COPD-ITPBS, COPD-ITASC, COPD-IVPBS and COPD-IVASC groups were exposed to cigarette smoke for 3 months and then received intratracheal or intravenous injection of PBS or ASCs. *<i>P</i><0.05 as compared with control group. ^#<i>P</i><0.05 as compared with COPD-ITPBS group.</p

Serum level of IL-8 in different groups of animals.

<p>The animals in COPD-ITPBS, COPD-ITASC, COPD-IVPBS and COPD-IVASC groups were exposed to cigarette smoke for 3 months and then received intratracheal or intravenous injection of PBS or ASCs. Data are shown as mean± SEM. *<i>P</i><0.05 as compared with control group. ^#<i>P</i><0.05 as compared with COPD-ITPBS group.</p

Total (A) and differential (B) WBC counts in BALF of different groups of animals.

<p>The animals in COPD-ITPBS, COPD-ITASC, COPD-IVPBS and COPD-IVASC groups were exposed to cigarette smoke for 3 months and then received intratracheal or intravenous injection of PBS or ASCs. Data are shown as mean± SEM. *<i>P</i><0.05, **<i>P</i><0.01 and ***<i>P</i><0.001 as compared with control group. ^#<i>P</i><0.05 and ^##<i>P</i><0.01 as compared with COPD-ITPBS group. ⁺⁺<i>P</i><0.01 as compared with COPD-IVPBS group.</p

Concentration of IL-8 in BALF of different groups of animals.

<p>The animals in COPD-ITPBS, COPD-ITASC, COPD-IVPBS and COPD-IVASC groups were exposed to cigarette smoke for 3 months and then received intratracheal or intravenous injection of PBS or ASCs. Data are shown as mean± SEM. *<i>P</i><0.05 as compared with control group. ^#<i>P</i><0.05 as compared with COPD-ITPBS group.</p

Fluorescence microscopic photographs of lungs after intratracheal or systemic delivery of CM-DiI-labeled stromal cells.

<p>(A) Image of lung from COPD animal harvested 14 days after injection of labeled cells into trachea. Magnification ×100; (B) Image of lung from COPD animal harvested 14 days after injection of labeled cells into jugular vein, Magnification ×400.</p

Cumulative concentration-response curves of methacholine induced trachea contraction.

<p>(A) Control and cigarette smoke exposed animals (an animal model of COPD); (B) COPD-ITPBS, COPD-ITASC, COPD-IVPBS and COPD-IVASC groups. The animals in COPD-ITPBS, COPD-ITASC, COPD-IVPBS and COPD-IVASC groups were exposed to cigarette smoke for 3 months and then received intratracheal or intravenous injection of PBS or ASCs.</p

The pattern and risk factors associated with adverse drug reactions induced by Reteplase in patients with acute ST-elevation myocardial infarction: The first report from Iranian population

Objective: Acute myocardial infarction (AMI) is one of the main leading causes of mortality and morbidity. Reteplase is a fibrin-specific thrombolytic which is used in the treatment of AMI. There is a limited number of studies reporting the postmarketing adverse drug reactions (ADRs) induced by reteplase. This study was aimed to examine the reteplase pattern of ADR and its associated risk factors in patients with acute ST-elevation myocardial infarction. Methods: A cross-sectional, prospective study in an 8-month period was done at the University affiliated referral cardiovascular center. The Naranjo probability scale and World Health Organization criteria for severity of ADRs were used for assessing the ADRs. The linear regression and logistic regression tests were used to evaluate the correlation between ADRs and risk factors. Findings: The all 20 patients who received reteplase during the study period were entered. The majority of patients (n = 17) experienced at least one ADR. The results showed that the incidence of ADRs was mainly associated with gender and age, and the number of ADRs was associated with the history of diabetes and taking anti-diabetic agents. The gender was the main predictor in the occurrence of ADRs (odds ratio: 32, 95% confidence interval: 1.38–737.45; P = 0.030). Conclusion: The results showed that gender, age, diabetes mellitus, and using of anti-diabetes medications are the risk factors associated with the incidence of ADRs by reteplase