3D organoid culturing devices to induce in vitro models of human intestinal inflammation

Abstract

Organoid culturing in microfluidic devices becomes an important technology for high throughput screening (HTS) of drugs, nutrients, and microbiome metabolites. Here, we present 3D organoid culturing devices to induce inflammation in human pluripotent stem cell (hPSC)-derived intestinal organoids (hIOs). Using high resolution 3D printing process, we established a method to fabricate microfluidic devices which have microchannels and 3D dome. The 3D dome geometry is suitable for the formation of Matrigel which serves as a cellular matrix. To validate the efficacy of the culturing devices, we induced inflammation in the hPSC-derived hIOs by the treatment of the combined proinflammatory cytokines such as interferon γ (IFNγ) and tumor necrosis factor α (TNFα). The inflamed hIOs have thinner epithelium with the upregulation of inflammatory cytokines. The induction of inflammatory models inside the 3D devices paves a way towards a microf luidic platform to investigate HTS.