Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice

Embryonic stem (ES) cells display the ability to differentiate in vitro int o a variety of cell lineages. Using a cell-trapping system, we have obtaine d an insulin-secreting cell clone from undifferentiated ES cells. The const ruction used allows the expression of a neomycin selection system under the control of the regulatory regions of the human insulin gene. The chimeric gene also contained a hygromycin resistance gene (pGK-hygro) to select tran sfected cells. A resulting clone (IB/3x-99) containing 16.5 ng/mu g protein of total insulin displays regulated hormone secretion in vitro in the pres ence of various secretagogues. Clusters obtained from this clone were impla nted (1 x 10(6) cells) in the spleen of streptozotocin-induced diabetic ani mals. Transplanted animals correct hyperglycemia within 1 week and restore body weight in 4 weeks. Whereas an intraperitoneal glucose tolerance test s howed a slower recovery in transplanted versus control mice, blood glucose normalization after a challenge meal was similar. This approach opens new p ossibilities for tissue transplantation in the treatment of type 1 and type 2 diabetes and offers an alternative to gene therapy.