ARTORG Center for Biomedical Engineering Research

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2022/08/17 | Research | In-vitro & Organs-on-Chip

Modelling lung injury and toxicity on chip

Debilitating lung health burdens like chronic obstructive pulmonary disease, acute respiratory distress syndrome, pulmonary fibrosis and acute lung injury call for more realistic human-cell-based in-vitro models to study pathomechanisms and the effect of toxins on the lung. The Organs-on-Chip Technologies lab of the ARTORG Center in collaboration with the Inselspital, the Helmholtz Center for Infection Research, Germany, and the Bernese start-up AlveoliX have now validated the first breathing model of the distal airways based on a novel primary-derived alveolar epithelial cell line (AXiAECs) on-chip (AXLung-on-chip, developed by AlveoliX).

AXLung-on-chip System includes the Lung-on-chip (AX12), two electro-pneumatic modules: AXExchanger and AXBreather, and the interface platform: AXDock (left). The AX12 includes two modular chips, where each alveolar unit comprises of an inlet and an outlet well, connected through microfluidic channels and pneumatic valves to the cell compartment (right). (Credit: Nuria Roldan, AlveoliX AG, Switzerland)

The impairment of the air-blood barrier is a hallmark event in fatal pulmonary condition. Hence, the development of therapeutic strategies to treat such chronic diseases requires robust preclinical in vitro models that mimic a disrupted alveolar barrier. This project characterized a novel distal airway model consisting of a new immortalized human alveolar epithelial cell line (AXiAECs) cultured in an in vivo-like alveolar microenvironment (AXLung-on-chip system) with regards to its alveolar character, reproducibility, robustness, and stability of culture conditions.

When culturing AXiAECs on-chip, the authors could see stable alveolar barrier function preserved across passages with increased trans electrical barrier resistance in both mono- and co-culture with endothelial cells. Moreover, AXiAECs cultured in physiological cell culture conditions of air-liquid interface (ALI) on-chip demonstrated enhanced barrier properties and alveolar characteristics. The organ-on-chip technology is able to replicate critical points of the dynamic alveolar microenvironment including 3D breathing motion (10% linear strain) (Stucki et al., 2018).

Disease modelling on chip

The team around the two first authors Arunima Sengupta, ARTORG Center, and Nuria Roldan, AlveoliX, analyzed different stages of alveolar damage including inflammation and the response to a profibrotic mediator as well as the expression of host cell factors involved in SARS-CoV-2 infection relevant for COVID19 studies.

(Credit: Arunima Sengupta, ARTORG Center, University of Bern)

The researchers plan on continuing to study inhalation-based toxicity with their model and to incorporate immune cells to study inflammation and its interplay in detail with barrier function, as well as its impact on cellular uptake of aerosolized nanoparticles. They are also working on nebulizing inhaled corticosteroids to study how it could alleviate nanoparticles-induced inflammation.

This research was financially supported by Lungenliga and Eurostars.