In diabetes, insulin-producing β cells, which are located within islets of Langerhans in the pancreas, are dysfunctional or destroyed by high levels of metabolites, such as glucotoxicity or lipotoxicity, or by autoimmune attack. These results provide a platform for evaluating the effects of the islet tissue microenvironment on human embryonic stem cell-derived β cells and other islet endocrine cells to develop tissue engineered islets. This assembly was not observed on traditional tissue culture plastic and in aggregates generated in suspension culture, highlighting how physical culture conditions greatly influence the interactions among these cell types. The resulting islet organoids express β cell and other endocrine markers and are functional, capable of undergoing glucose-stimulated insulin secretion. We have developed a strategy of assembling human embryonic stem cell-derived islet cells with endothelial cells into three-dimensional aggregates on a hydrogel. Despite the potential importance of endothelial cells to islet function, facilitating interactions between endothelial cells and islet endocrine cell types already differentiated from human embryonic stem cells has been difficult in vitro. The islets of Langerhans contain many endocrine and non-endocrine cell types, such as insulin-producing β cells and endothelial cells. However, one limitation has been organization of differentiated cells into multi-cellular, three-dimensional assemblies. Differentiation of stem cells into functional replacement cells and tissues is a major goal of the regenerative medicine field.

Dead cells face flask