Human Cellular Models for the Investigation of Lung Inflammation and Mucus Production in Cystic Fibrosis.
Stefano CastellaniSante Di GioiaLorena di TomaMassimo ConesePublished in: Analytical cellular pathology (Amsterdam) (2018)
Chronic inflammation, oxidative stress, mucus plugging, airway remodeling, and respiratory infections are the hallmarks of the cystic fibrosis (CF) lung disease. The airway epithelium is central in the innate immune responses to pathogens colonizing the airways, since it is involved in mucociliary clearance, senses the presence of pathogens, elicits an inflammatory response, orchestrates adaptive immunity, and activates mesenchymal cells. In this review, we focus on cellular models of the human CF airway epithelium that have been used for studying mucus production, inflammatory response, and airway remodeling, with particular reference to two- and three-dimensional cultures that better recapitulate the native airway epithelium. Cocultures of airway epithelial cells, macrophages, dendritic cells, and fibroblasts are instrumental in disease modeling, drug discovery, and identification of novel therapeutic targets. Nevertheless, they have to be implemented in the CF field yet. Finally, novel systems hijacking on tissue engineering, including three-dimensional cocultures, decellularized lungs, microfluidic devices, and lung organoids formed in bioreactors, will lead the generation of relevant human preclinical respiratory models a step forward.
Keyphrases
- cystic fibrosis
- oxidative stress
- inflammatory response
- immune response
- endothelial cells
- pseudomonas aeruginosa
- dendritic cells
- induced pluripotent stem cells
- tissue engineering
- lung function
- drug discovery
- induced apoptosis
- stem cells
- pluripotent stem cells
- toll like receptor
- lipopolysaccharide induced
- dna damage
- high throughput
- cell proliferation
- signaling pathway
- mesenchymal stem cells
- wastewater treatment
- circulating tumor cells
- multidrug resistant
- endoplasmic reticulum stress
- lps induced