Novel Three-Dimensional Organoid Sarcoidosis Granuloma Model

Abstract

Sarcoidosis is a multi-system disorder of granulomatous inflammation which most commonly affects the lungs. Its etiology and pathogenesis are not well defined in part due to the lack of reliable modeling. This article presents the development of a novel in vitro three-dimensional lung-on-chip organoid designed to mimic granuloma formation. A lung on chip fluidic macrodevice with three channels for cell culture insertion was developed and added to the previously developed a lung-on-membrane model. Granulomas were cultured from blood samples of patients with sarcoidosis and then inserted in the air-lung-interface (ALI) of the microchip to create a three-dimensional organoid sarcoidosis model (OSGM). The model was tested for cell viability with fibroblasts. We measured the cytokine profiles in medium of OSGM and compared with lung model without granuloma. Concentration of IL-1beta, Il-6, GM-CSF, and IFN-gamma were found significantly higher in OSGM group. The current model represents the first 3D OSGM created by adding a microfluidics system to a dual-chambered lung on membrane model and introducing developed sarcoid-granuloma to its ALI.