Microbial volatile communication in human organotypic lung models

Abstract

We inhale respiratory pathogens continuously, and the subsequent signaling events between host and microbe are complex, ultimately resulting in clearance of the microbe, stable colonization of the host, or active disease. Traditional in vitro methods are ill-equipped to study these critical events in the context of the lung microenvironment. Here we introduce a microscale organotypic model of the human bronchiole for studying pulmonary infection. By leveraging microscale techniques, the model is designed to approximate the structure of the human bronchiole, containing airway, vascular, and extracellular matrix compartments. To complement direct infection of the organotypic bronchiole, we present a clickable extension that facilitates volatile compound communication between microbial populations and the host model. Using Aspergillus fumigatus, a respiratory pathogen, we characterize the inflammatory response of the organotypic bronchiole to infection. Finally, we demonstrate multikingdom, volatile-mediated communication between the organotypic bronchiole and cultures of Aspergillus fumigatus and Pseudomonas aeruginosa.

Stem cell-based Lung-on-Chips: The best of both worlds?

“…Alternative on-chip systems of the human airway epithelium include a triple channel chip design where an additional compartment containing fibroblasts is inserted between the epithelial and vascular channels [128,131]. This configuration, however, so far does not support full differentiation of the human primary airway epithelial cells but remains promising for investigating cross communication between the three different cell populations and their respective influence on each other's growth and differentiation.…”

Advanced Microengineered Lung Models for Translational Drug Discovery

“…28 Most recently, Barkal et al engineered a microscale fluidic organotypic model of the human bronchiole to examine inflammatory responses to respiratory fungal pathogens. 101 The authors developed a complex multicellular platform that contained primary human bronchial epithelium, tightly packed lung microvascular endothelium, fibroblasts, ECM, and whole-blood extracted neutrophils. The microsystem enabled real-time analysis of leukocyte extravasation and migration through the endothelial layer and collagen matrix toward fungal hyphae during infection, and it allowed study of airway response to microbial volatiles.…”

Disrupting Experimental Strategies for Inhalation Toxicology: The Emergence of Microengineered Breathing-Smoking Human Lung-on-a-Chip

“…Table 1 summarizes key aspects of this platform and its comparison against airway microphysiological models developed by other groups. [30][31][32][33] In a follow-up study, the same research team elegantly reverses engineered design principles of an average smoker's lung to create a ''Breathing-Smoking Human Lung-on-a-Chip'' in vitro (Fig. 1).…”

“…Device contained an open top chamber (airway) and a bottom fluidic channel (blood vessel) that had a depth of 1500 lm.Cultures on-chip were maintained viable for up to 10 days.Organotypic human bronchiole (Barkal et al33 …”