Modelling of Beta Cell Pathophysiology Using Stem Cell-Derived Islets

Diabetes mellitus is a family of metabolic disorders that arise from the loss or dysfunction of insulin secreting pancreatic beta cells. Many forms of early onset diabetes are caused by monogenic mutations in genes with critical roles in pancreatic development and endocrine cell function. Stem cell-derived islets (SC-islets) represent a powerful tool by which to dissect the mechanisms of human beta-cell loss and dysfunction derived from these causative mutations in a reproducible in vitro model. While still in its relative infancy, SC-islet modelling has successfully recapitulated many elements of monogenic pathologies in mutations related to neonatal diabetes, maturity onset diabetes of the young (MODY), and even polygenic and multi-tissue models of type 1 diabetes. In this chapter, we outline the progress that has been made in applying SC-islet technologies to multiple forms of monogenic diabetes, as well as discuss the limitations and possibilities of SC-islets in comparison to other contemporary beta-cell modelling systems.