Inflammation is an essential component of many lung diseases, including asthma, COPD, lung cancer, and pathogenic infections. While excessive inflammation causes lung injury, without adequate inflammation there is no protection against pathogenic infections. Airway mucus is an important component in the airway defense against pathogens as well as regulator of inhaled agent penetration. Consequently, muscus production is an important element of key pathophysiological features of asthma, COPD and cystic fibrosis (CF).
Humeltis’s proprietary immune cell containing 3D aggregate and sandwich models mimic specific physiological mechanisms of the bronchial and alveolar structures of the human lung. Our unique model systems enable Humeltis to perform studies in drug response, airway remodeling as well as exposures to environmental pollutants, including cigarette smoke, car exhausts etc.
Exposure to cigarette smoke
Although the genetic background is important to disease development, e.g. in COPD cigarette smoking is the most important risk factor. Toxins and particulate matter in inhaled smoke induce acute inflammation in the airways. With repeated smoke exposure, inflammation becomes chronic and damages the airway epithelium and lung tissue which leads to remodeling of the respiratory tissues. Our model tissues can be exposed to cigarette smoke using accepted standardized conditions (Figure 1).
Epithelial barrier function
Maintenance of epithelial barrier function is critical for maintaining the healthy state of the respiratory mucosa. Loss-of-barrier function as a result of mucosal inflammation contributes to progression to chronic disease conditions. In vitro studies examining the effects of cigarette smoke extract on primary bronchial or alveolar epithelial cells have shown that the endogenous proteases mediate degradation of tight junction complexes. Our immune cell containing sandwich models are particularly suitable for such studies.
Pro-inflammatory cytokine production
Noxious fumes, cigarette smoke, etc induces pro-inflammatory cytokine and chemokine production in the respiratory tract as well as in resident immune cells (Figure 2). The secreted small molecules can be measured by mRNA level changes in the cells of the model tissues and commercially available cytokine arrays directly from the culture medium. The model tissues can also be sectioned and intra cellular, cell surface and secreted protein changes can be tested using microscopy techniques (Figure 3).