Project description:Background: Chronic obstructive pulmonary disease (COPD) is a serious chronic disease of the airways that affects many people worldwide and have limited treatment options. While small animal models provide a platform for therapeutic investigations into COPD, their deficiencies continue to impede clinical translation. Alternatively, as a large animal model, sheep have a respiratory system anatomically and physiologically similar to that of humans, encouraging their use in airway disease research. The aim of this study was to better understand disease pathology in a large animal (sheep) experimental model of COPD. Methods: COPD was induced in sheep following lung exposure to porcine elastase (PE) and repeated weekly lung exposures to lipopolysaccharide (LPS) over a period of 8 weeks. Bronchoalveolar fluid and blood samples were collected for immune analyses. Lung function was assessed and lung tissues were collected for histopathology and RNA sequencing. Results: Lung neutrophil levels were elevated in response to repeated airway exposure to PE/LPS, accompanied by a significant decline in ventilation over time. Histological evidence of COPD-like disease changes included chronic inflammation with increased airway and tissue inflammation scores, together with significantly larger airway wall area measures, increased connective tissue deposition and dysregulated gene expression. Conclusions: These studies demonstrate sustained chronic airway inflammation and pathophysiological lung changes in a sheep model of COPD, providing many similarities to that seen in COPD patients. This work opens a pathway for future translational studies using this unique large animal model of COPD, which will serve to bridge the gap between smaller animal models and humans.
Project description:Recently, we described a new animal model of CNS primitive neuroectodermal tumors (CNS-PNET), which was generated by orthotopic transplantation of human Radial Glial (RG) cells into NOD-SCID mice’s brain sub- ventricular zone. In the current study we conducted comprehensive RNA-Seq analyses to gain some insights on the mechanisms underlying tumorigenesis in this mouse model of CNS-PNET. Here we show that the RNA-Seq profiles derived from these tumors cluster with those reported for patients’ PNETs.