).Diabetes (either type 1 or type 2) is due to insufficient functional β-cell mass. Research has, therefore, aimed to discover new ways to maintain or increase either β-cell mass or function.For this purpose, rodents have mainly been used as model systems and a large number of discoveries have been made. Meanwhile, although we have learned that rodent models represent powerful systems to model β-cell development, function and destruction, we realize that there are limitations when attempting to transfer the data to what is occurring in humans. Indeed, while human β-cells share many similarities with rodent β-cells, they also differ on a number of important parameters. In this context, developing ways to study human β-cell development, function and death represents an important challenge. This review will describe recent data on the development and use of convenient sources of human β-cells that should be useful tools to discover new ways to modulate functional β-cell mass in humans. K E Y W O R D Sβ-cells, β-cell lines, GPR68, human, pancreatic, RFX6, stem cells | INTRODUCTIONβ-Cells are rare specialized cells devoted to produce large amounts of insulin that is stored within granules and secreted in a tightly regulated fashion. 1 In the pancreas, β-cells are clustered, forming micro-organs, named the islets of Langerhans. A human pancreas contains around 1 million islets and each islet contains hundreds of β-cells. 2 Due to their stochastic spatial distribution, imaging human pancreatic islets in vivo remains extremely challenging. 3 Human islet purification from cadaveric donors is possible, but quantitatively limited, with major variation in terms of purity from one preparation to another. 4 In the past, we have learned a lot about β-cells using animal models, primarily rat and mouse.In such species, islets can be prepared from which β-cells are purified and studied in great detail. By performing comparative analyses, however, we have learned that while rodent and human β-cells share many similarities, they also differ on a number of important parameters. 5,6 In this context, developing ways to analyse human β-cells in great detail currently represents a major challenge.In this review, we will summarize our knowledge on similarities and differences between rodent and human β-cells. We will next concentrate on the different human β-cell sources that can be used to study this specific cell type. | SIMILARITIES AND DIFFERENCES BETWEEN RODENT AND HUMAN β-CELLSPancreatic β-cells can be considered as factories whose major task is to produce huge amounts of insulin (more than 20% of β-cell mRNA codes for insulin) 7 that is stored and secreted upon specific stimulation. During the past years, we have learned that while rodent β-cells represent an extremely useful model to approximate human β-cells, more remains to be learned by directly working on human β-cells. Indeed, rodent and human β-cells share many similarities, but also a number of differences. As a first example, two genes encode insulin in rodents (both rats...