Non Animal Testing Database

Bronchial chip reveals the interplay of mechanical and biochemical signals in bronchospasm

Johns Hopkins Bloomberg School of Public Health, Baltimore, USA(1)
Johns Hopkins University, Baltimore, USA(2)
In asthma, airway smooth muscle contraction and subsequent airflow reduction are associated with a series of poorly understood mechanical and biochemical events. Here, the researchers present a microphysiological bronchial chip airway model that allows quantitative analysis of the interactions between mechanical and biochemical signals triggered by pressure loading of epithelial cells. 3D cocultures of primary human airway smooth muscle cells (HASM) and healthy human bronchial epithelial cells (NHBE) fully differentiated in an air-liquid interface were used for this purpose. By using a technique that reduces the lateral intercellular space of the pseudostratified NHBE layer, pressure loading was allowed from apical to basal, thereby mimicking severe bronchospasm. The resulting changes in the mechanical properties of HASM cells were quantitatively measured in real-time by cytometry. This mechanistic model allows the explanation of a rapid, switch-like triggering of bronchospasm by the secretion of spasmogenic factors due to compressed epithelial airway cells acting on ASM cells, promoting their further contraction and thus forming a putative feedback loop. Also, the method provides information about delayed negative feedback that may trigger the relaxation in bronchospasm.
A microphysiological model of the bronchial airways reveals the interplay of mechanical and biochemical signals in bronchospasm
Onur Kilic(1), Steven S. An(1), Andre Levchenko(2)
Added on: 08-22-2022
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