Hydrogel platform for in vitro three-dimensional assembly of human stem cell-derived β cells and endothelial cells

Abstract Differentiation of stem cells into functional replacement cells and tissues is a major goal of the regenerative medicine field. However, one limitation has been organization of differentiated cells into multi-cellular, three-dimensional assemblies. The islets of Langerhans contain many endocrine and non-endocrine cell types, such as insulin-producing β cells and endothelial cells. Transplantation of exogenous islets into diabetic patients can serve as a cell replacement therapy, replacing the need for patients to inject themselves with insulin, but the number of available islets from cadaveric donors is low. We have developed a strategy of assembling human embryonic stem cell-derived β cells with endothelial cells into three-dimensional aggregates on a hydrogel. The resulting islet organoids express β cell markers and are functional, capable of undergoing glucose-stimulated insulin secretion. 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.