Bioengineered multi-organoids system from hiPSCs to recapitulate human islet-liver axis in health and diseas

In this work, we proposed a new and high through-put microfluidic multi-organoid-on-chip system that allow to recapitulate human liver-islet axis from induced pluripotent stem cells (hiPSCs). The generated pancreatic islet and liver organoids initiated in 3D culture and differentiated into organ-specific lineages with structures and functions of native counterparts. The microfluidic device consists of two culture chambers with arrays of micro-wells and several connector micro-channels and provided circulating fluid by perfusion apparatus. This perfused system enabled the exchange of secretion hormones and metabolic product between the two kinds of organoids. The co-cultured liver and islet organoids exhibited improved cell viability, secretion function and organ-specific markers during the long-term culture period. Moreover, this multi-organoid system showed more sensitive glucose-stimulated insulin secretion of islet and glucose utilization of liver organoids. In addition, this platform could to model pathological features of high glucose induced damage in liver and islet organoids and in favor of metformin treatment effect.