This study describes a novel alveolar in-vitro model, that combines a human-derived immortalized cell line and organ-on-chip technology mimicking the lung alveolar biophysical environment. Key features of the in-vivo alveolar milieu are simulated, by integrating breathing-like 3D cyclic stretch and an ultrathin, porous and elastic membrane, as well as by culturing at the air-liquid interface (ALI).
Human alveolar cells cultured on the chip were characterized, and cell barrier properties were examined by analysis of transbarrier electrical resistance. Alveolar damage including inflammation was investigated via exposure to bacterial lipopolysaccharide, and the response to a profibrotic mediator was analyzed. The results demonstrate that the developed lung-on-a-chip system exhibits an enhanced alveolar character, and facilitates reproducible long-term preservation of alveolar characteristics in nearly physiological conditions (co-culture, breathing, ALI).
This lung model thereby represents a valuable in-vitro tool to study inhalation toxicity and to test the safety and efficacy of drug compounds.
A new immortalized human alveolar epithelial cell model to study lung injury and toxicity on a breathing lung-on-chip system
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