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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - EpiCBiome (Development of an innovative Airway-on-Chip microbiome cell culture model to investigate host-microbiome interactions at the airway epithelial surface)

Teaser

Summary

Chronic Obstructive Pulmonary Disease (COPD) is a progressive chronic lung disease characterized by development of irreversible loss of lung function and persistent lung inflammation. In addition, patients with COPD have a higher frequency of respiratory infections, which are considered to be main triggers for exacerbations (â€œlung attacksâ€). Exacerbations accelerate disease progression, reduce quality-of-life and are associated with substantial mortality. Despite extensive efforts to find an effective cure by the international scientific community and pharmaceutical companies, treatment of COPD is limited to symptom reduction and prevention of further deterioration of lung quality. Alarmingly, today COPD represents the third cause of death worldwide. These dramatic statistics underscore the need to better understand COPD in order to identify new and effective therapeutic strategies. One such strategies may lie in the airway microbiota. Similar to the gut, also the airways harbour a variety of microorganisms that have a unique composition called the airway microbiota. In the gut it was shown how important the composition of this microbiota is as disturbances could be linked to disease. Much less is known about the contribution of airway microbiota to health or disease. Interestingly, in patients with chronic inflammatory lung diseases the composition of the airway microbiota has changed and it is currently unclear why these changes have occurred and if and how these changes affect disease progression.

Using a unique human cell culture model, a lung-on-a-chip, interactions between the human airways and resident bacteria will be studied. In this model, the airway epithelial cells are cultured that line the airways and are in the lung are close contact with inhaled substances and with the airway microbiota. The researcher aims to elucidate if changes in airway epithelial composition drive changes in the airway microbiota. In addition, it will be tested if airway microbiota from patients with chronic lung diseases affect airway epithelial biology different than that of healthy controls.

This knowledge will be of significant importance as it potentially will contribute to the development of more effective healthcare strategies that are currently lacking for COPD.

Work performed

This full first year of the granted period was spent by the researcher at the organ-on-chip company Emulate Inc. Boston, MA, U.S.A. to obtain hands-on experience with their organ-on-chip platform. At Emulate, routine was developed by the researcher by working with the lung-chip and several pilot experiments were performed to develop a protocol for a stable long-term co-culture between airway epithelial cells and microbiota. After one year, Emulateâ€™s organ-on-chip platform was installed at the Leiden University Medical Center to continue studies in the Netherlands that will focus now on finalizing the protocol for the co-culture and additionally performing experiments with co-cultures using healthy airway epithelium and cultures of which differentiation of the epithelium was modulated, representing diseased lungs.

Final results

It is expected that at the end of the granted period there is a robust airway epithelial-microbiota co-culture model protocol. In addition, we anticipate that we can show results on how altered differentiation of the airway epithelium affects microbiota composition and can elucidate if the main factor behind exacerbated inflammatory responses of patients with chronic inflammatory disease to exposures is predominantly driven by the epithelial side or by changes in the microbiota (or both). These results define the relevance of studying airway microbiota-host interactions in chronic inflammatory diseases and will provide a protocol to study these in detail. These results will therefore impact on the academic developments in this field and hopefully in the future will also contribute to initiatives that lead to new therapeutics.