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MOC system of the liver-islet axis in normal and type 2 diabetes

December 2021
Chinese Academy of Sciences, Dalian, China
Type 2 diabetes mellitus (T2DM) is a systematic multi-organ metabolic disease, which is characterized by the dynamic interplay among different organs. The increasing incidence of T2DM reflects an urgent need for the development of in vitro human-relevant models for disease study and drug therapy. Here, a new microfluidic multi-organoid system is developed that recapitulates the human liver-pancreatic islet axis in normal and disease states. The system allows 3D co-culture of human iPSC-derived liver and islet organoids for up to 30 days under circulatory perfusion conditions. The co-cultured liver and islet organoids exhibit favourable growth and improved tissue-specific functions. Notably, the co-culture system facilitates sensitive glucose-stimulated insulin secretion from islet organoids and increased glucose utilization in liver organoids by glucose tolerance tests. Both liver and islet organoids display mitochondrial dysfunction and decreased glucose transport capacity under high glucose conditions, which can be alleviated by metformin treatment. This novel multi-organoid system can recapitulate the human-relevant liver-islet axis under both physiological and pathological conditions, providing a unique platform for future T2DM research and drug development.
Microengineered multi-organoid system from hiPSCs to recapitulate human liver-islet axis in normal and type 2 diabetes
Jianhua Qin
#1364
Added on: 03-10-2022
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