In what areas the in vitro models can help the researchers to move forward?
Cystic fibrosis is a genetic disease whose treatment has not yet been found. New drugs have been developed which improve the health of cystic fibrosis patients. Reconstituted in vitro human epithelial models contribute significantly to the development of these new drugs, since the respiratory system is the most affected organ by this disease. In fact, in the patients with cystic fibrosis, the mucus in the airways are very viscous and sticky which cannot be cleared by mucociliary clearance. As consequence, the clogged airways are infected and colonized by microbes, leading to chronic inflammation. This phenomenon is reproduced in in vitro lung tissues, making it possible to test the efficacy of the drugs or gene therapy to restore mucociliary function.
Although asthma is an inflammatory disease, symptoms often occur mainly at the respiratory level. Indeed, for asthmatic patients, the epithelium is altered and weakened. Because lung epithelial cells also communicate with immune cells, infection of the respiratory epithelium by microbes contributes to the exacerbation of asthma. In vitro respiratory tissues allow to test new therapeutic approaches, such as new local anti-inflammatory drugs. The epithelium is a very effective and promising immuno-regulator for detecting new allergens. Its use can allow to detect and identify potential allergens.
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Chronic obstructive pulmonary disease (COPD) is characterized by progressive degeneration of lung tissue and obstruction of the airways. In vitro lung tissue can be used to model metaplasia and to visualize deregulated markers in COPD patients.
Pseudomonas aeruginosa, Streptococcus pneumonia, Staphylococcus aureus, these bacteria can infect the respiratory system through inhalation. Infection with these bacteria is considered as a serious health concern by the World Health Organization. So, it is necessary and urgent to develop new antibiotics to overcome the problem of antibiotic-resistance. Human respiratory tissues, being the first target of bacteria, is an efficient platform to test the efficacy of new antibiotics.
Many viruses are capable of infecting the respiratory epithelium, including influenza, rhinovirus, syncytial respiratory virus, coronavirus, metapneumovirus, etc. These viruses enter the cells through receptors and replicate inside the pulmonary tissues. In vitro airway tissues are very powerful research tools to study the mechanism and mode of action of viral infection and thus it helps us to develop new antiviral drugs.
IMPACT OF AIR POLLUTANTS
Respiratory tissues are the first line of defense against the air pollutants. The acute but also chronic local effect, such as inflammatory, cytotoxic or remodeling effect of these inhaled substances can be observed and quantified using in vitro lung models.