Abstract
The pancreas is a complex and highly specialized organ, whose main function is to maintain glucose homeostasis in the body. This homeostasis is regulated by the endocrine compartment of the pancreas. Multiple potential molecular and metabolic perturbations occurring in these cells may result in a wide spectrum of disorders. The study of the pancreas to dissect the underlying mechanisms of pathology has been challenging, owing to the lack of adequate biological models. This caveat has been recently addressed by the generation of organ-like structures (“organoids”) and artificial constructs that aim at mimicking the cytoarchitecture of the pancreas. Advances in our understanding of how the pancreas forms during embryonic development have provided us with insights on how to direct differentiation toward the formation of endocrine cells. In vitro differentiated endocrine cells, for instance, may be used to treat pancreatic disorders such as insulin-dependent diabetes and as a screening tool for potential therapies. This approach has progressively displaced the use of islets isolated from cadaveric donors, a material of scarce availability and broad donor-related variability. In fact, human embryonic stem cell (hESc)-derived islets are currently in clinical trials for type 1 diabetes. This short review discusses the current state of the art in the generation of renewable sources of pancreatic endocrine cells, with a special emphasis in future therapeutic applications.