Organ-on-Chip Meets Immunology: Let’s Start with the Lungs

Abstract Organs-on-chips are biomimetic, microfluidic, cell culture devices created with microchip manufacturing methods that contain continuously perfused hollow microchannels inhabited by living tissue cells arranged to simulate organ-level physiology. By recapitulating the multicellular architectures, tissue-tissue interfaces, chemical gradients, mechanical cues, and vascular perfusion of the body, these devices produce levels of tissue and organ functionality not possible with conventional 2D or 3D culture systems. They also enable high-resolution, real-time imaging and in vitro analysis of biochemical, genetic and metabolic activities of living human cells in a functional human tissue and organ context. Here, we discuss development of ‘Human Lung Small Airway-on-a-Chip’ – an engineered cell-by-cell reconstituted microfluidic device with living human tissues to model airway inflammation in the context of debilitating lung diseases, including asthma and chronic obstructive pulmonary disease (COPD). In addition, we will present our preliminary data on recreating a hematopoietically active bone marrow niche in vitro (‘BM-on-a-Chip’) for microphysiological integration with the Small Airway-on-a-Chip to emulate innate immune cell egress into circulation (from the BM) and their recruitment to the lung airway.