Figure 3

R1Pdx1AcGFP ES cell-derived IPCs correct hyperglycemia in diabetic mice. (a) The therapeutic efficacy of R1Pdx1AcGFP/RIP-Luc ES cell-derived IPCs was evaluated following transplantation under the kidney capsule of syngeneic 129/SvJ mice (n = 12) rendered diabetic by streptozotocin (STZ) treatment. The blood glucose levels continued to decline beyond Day 15 post-transplantation and stabilized thereafter. Normal nondiabetic mice (n = 5) and STZ-treated 129/SvJ mice (n = 5) were used as appropriate controls for comparing the blood glucose levels. As early as Day 15 and throughout the duration of the study, the blood glucose levels of mice transplanted with IPCs were significantly lower compared to the STZ-treated mice. The data were analyzed by one-way ANOVA and are presented as mean ± SD, ***P < 0.0001, using Tukey’s pairwise multiple comparison for Day 15. (b) The kidney bearing the transplanted IPCs was evaluated for insulin expression by immunostaining using an anti-insulin antibody. The results indicate the localized presence of ES cell-derived insulin expressing cells. (c) Control mouse pancreas and the pancreas from IPCs transplanted mice 150 days post transplantation were examined by hematoxylin-eosin staining. Unlike control pancreas from non-diabetic mouse, the IPCs transplanted streptozotocin-treated diabetic mouse pancreas did not show any evidence of pancreatic beta cell regeneration.