Generating mature β-cells from embryonic stem cells: strategies for late-stage differentiation.

Generation of mature pancreatic β-cells from embryonic stem (ES) cells in vitro could provide a therapy for insulin-dependent diabetes mellitus. Recent ES cell differentiation protocols have improved the differentiation efficiency toward β-cells by recapitulating in vivo pancreatic development. Toward this end, there is a large number of developmental and β-cell functional studies that could guide the design of more efficient differentiation protocols, predominantly during the late stages. In this review, I have classified these studies according to the intracellular signaling pathways they relate to--phosphatidylinositol 3-kinase, Hedgehog, Calcineurin/NFAT, Epac, and bone morphogenetic protein.