Research Focus: Human Microphysiological Lung-on-a-Chip.

Advances in microphysiological organ-on-chip technologies have enabled spatiotemporal investigation into the biology of organ systems in healthy and disease-like conditions in vitro. The highly-tunable nature of on-chip models permit direct manipulation of the microenvironment and provides the framework to study disease progression in a way not feasible through other in vitro or in vivo models. In our lab, we have developed a two-layer human lung-on-chip (LOC) device to study the lung immune landscape. Our LOC device consists of an interstitial niche with perfusable microvasculature, lung fibroblasts, and resident immune cells, and an epithelial layer at air-liquid interface separated by a membrane. The devices are fabricated in a 96-well format to increase throughput and allow for integration with liquid handling and automated imaging tools.

Current work aims to incorporate circulating immune cells and tissue-specific macrophage populations to model systemic and mucosal immunity and their interactions. This immune-competent LOC device can then be used to model various immunopathologies of the lung to better understand both disease progression and response to therapeutics. Currently, the LOC is used to model influenza A infection and determine the contributions of both tissue-resident and circulating immune cells to the overall coordinated immune response. In this model, we are able to study a hyperactive, pro-inflammatory immune landscape. We are also utilizing the LOC to study the immune landscape in the context of lung cancer, with the goal of better understanding key drivers of the immunosuppressive tumor microenvironment and identifying potential treatment avenues. Thus, the LOC device can serve as a powerful tool to study both ends of the immune activation spectrum.