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A microphysiological model for the study of bronchial spasms

A microphysiological model of the bronchial airways reveals the interplay of mechanical and biochemical signals in bronchospasm

This issue highlights microphysiological systems of the human bronchial airways, the human gut microbiome, a glioblastoma tumour and cartilage, as well as an in vitro model of the formation of bone-like nodules recapitulating the osteogenesis-imperfecta phenotype, and a comparison of three congruent patient-specific cell types for the modelling of an inherited neurological disorder.

The cover shows a sham device of a microphysiological system that recapitulates the mechanochemical environment of the human bronchial airways.

See Kilic et al.

In asthma, the contraction of the airway smooth muscle and the subsequent decrease in airflow involve a poorly understood set of mechanical and biochemical events. Organ-level and molecular-scale models of the airway are frequently based on purely mechanical or biochemical considerations and do not account for physiological mechanochemical couplings. Here, we present a microphysiological model of the airway that allows for the quantitative analysis of the interactions between mechanical and biochemical signals triggered by compressive stress on epithelial cells. We show that a mechanical stimulus mimicking a bronchospastic challenge triggers the marked contraction and delayed relaxation of airway smooth muscle, and that this is mediated by the discordant expression of cyclooxygenase genes in epithelial cells and regulated by the mechanosensor and transcriptional co-activator Yes-associated protein. A mathematical model of the intercellular feedback interactions recapitulates aspects of obstructive disease of the airways, which include pathognomonic features of severe difficult-to-treat asthma. The microphysiological model could be used to investigate the mechanisms of asthma pathogenesis and to develop therapeutic strategies that disrupt the positive feedback loop that leads to persistent airway constriction.

Nature Biomedical Engineering volume 3pages532–544 (2019)

 

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