The comparative cell physiology of stem cell-derived and primary human β cells

The ability to generate stem cell-derived pancreatic β (SCβ) cells and stem cell-derived islets has opened new opportunities for type 1 diabetes mellitus therapies and disease modelling. Carefully assessing how closely SCβ cells resemble their primary counterparts is crucial to the support of ongoing clinical trials and human-centric studies on diabetes pathophysiology. Observed differences between SCβ cells and primary human β cells are generally attributed to the incomplete maturation of SCβ cells in vitro. However, even cells further matured in vivo can differ considerably from mature primary islet cells. In this Review, we examine key features of human β cells and islets, and summarize our current knowledge of these features in stem cell-derived products. We highlight knowledge gaps and discuss the requirements for comparative studies, emphasizing the importance of tissue quality, harmonizing approaches, integrating datasets and data sharing.