Stem cells and the endocrine pancreas.

BACKGROUND Diabetes can be treated by β-cell replacement therapy but the supply of graft material from human donors is too limited to make a significant clinical impact. Substitute β-cells generated from stem cell populations offer a potential source for the large numbers of cells required. SOURCES OF DATA Primary peer-reviewed reports of experimental studies. AREAS OF AGREEMENT Embryonic stem cells and/or induced pluripotent stem (iPS) cells are currently the most promising starting populations from which to generate large numbers of β-cells. Differentiation protocols that recapitulate in vivo development generate insulin-expressing cells in vitro. AREAS OF CONTROVERSY Differentiation outcomes may depend on the source of the initial pluripotent cells. The insulin-expressing cells are not fully functional. In vivo maturation is inconsistent and not well understood. AREAS TIMELY FOR DEVELOPING RESEARCH Improvement of current protocols for complete in vitro differentiation to a functional β-cell phenotype. Systematic analysis to identify the most appropriate starting material. Improved purification methods to ensure safety of material for clinical transplantation.