The present application discloses cell clusters resembling the function and characteristics of endogenous pancreatic islets, and methods for making and using such cell clusters. The present disclosure provides an in vitro cell cluster comprising at least one non-native pancreatic ß cell that exhibits an in vitro glucose-stimulated insulin secretion response when exposed to a glucose challenge, wherein the cell cluster is an unsorted cell cluster, and wherein the cell cluster comprises: at least 35% of cells that express NKX6.1 and C-peptide； at least 70% of cells that express chromogranin A； at most about 2% of cells that express SOX2； or at most about 10% of cells that express SOX9. In some cases, when transplanted into a subject, the in vitro cell cluster exhibits an in vivo glucose-stimulated insulin secretion response to a glucose challenge in the subject.
