Insulin production by human embryonic stem cells

Type 1 diabetes generally results from autoimmune destruction of pancreatic islet beta -cells, with consequent absolute insulin deficiency and complet e dependence on exogenous insulin treatment. The relative paucity of donati ons for pancreas or islet allograft transplantation has prompted the search for alternative sources for beta -cell replacement therapy. In the current study, we used pluripotent undifferentiated human embryonic stem (hES) cel ls as a model system for lineage-specific differentiation. Using hES cells in both adherent and suspension culture conditions, we observed spontaneous in vitro differentiation that included the generation of cells with charac teristics of insulin-producing beta -cells. Immunohistochemical staining fo r insulin was observed in a surprisingly high percentage of cells. Secretio n of insulin into the medium was observed in a differentiation-dependent ma nner and was associated with the appearance of other beta -cell markers. Th ese findings validate the hES cell model system as a potential basis for en richment of human beta -cells or their precursors, as a possible future sou rce for cell replacement therapy in diabetes.