Generation of functional human ipsc-derived pancreatic islets in co-culture with isogenic ipsc-derived vascular endothelial cells

Abstract

Diabetes is a clinical condition that affects millions of people worldwide, and is treated by insulin replacement therapies. New strategies to create scalable and compatible pancreatic islets containing insulin-producing beta cells are necessary as an alternative to limited supply of cadaveric islets or multiple exogenous insulin applications. Improvements are still necessary since many immature polyhormonal cells remain, and cannot attain a monohormonal state. During human development, pancreas co-develops with endothelium and shares signals, allowing for better maturation of beta cells, and this is not included in the current differentiation protocols. The organchip microfluidic devices allows dynamic co-culture of different cells, thus resembling in vivo physiology. Here the Inventors establish organ-chip models co-culturing human iPSC-derived pancreatic precursors with iPSC-derived endothelial cells to obtain more functional and monohormonal iPSC-derived beta cells.

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