Engineering a Human Microphysiological System for the Characterization of Islet-Immune Interactions

Project Narrative Three dimensional (3D) microphysiological systems (MPS) represent a powerful intermediate model system capable of bridging in vitro studies and clinical trials. We propose to create an integrated MPS platform to more accurately model the complex cellular interactions involved in human type 1 diabetes (T1D) pathogenesis. This effort will integrate prior efforts of CMAI and CHIB investigators to create an integrated islet:immune interface, referred to as the iiCHIP, employing technologies that facilitate testing of antigen-specific T cells, isogenic cellular systems capable of deriving multiple cellular lineages, and genome editing technologies to enable mechanistic studies capable of expediting clinical interventions aimed at inducing immune regulation and β-cell restorative therapies.