Figure 3.

Transplantation of Pancreatic Endoderm Cells Establishes and Maintains Normoglycemia in Diabetic B6/Rag^−/− Mice

(A) The proportion of animals that achieved euglycemia was similar in fat pad recipients (FP, purple, n = 6 mice) and unmodified subcutaneous recipients (SQ, red, n = 6 mice) post transplant, whereas all device-less recipients (DL, black, n = 22 mice) reversed diabetes (^∗∗p < 0.01, log rank, Mantel-Cox test).

(B, D, and F) Non-fasting blood glucose measurements showed that recipients of PECs transplanted into both FP (n = 4 of six mice) and SC space (n = 4 of six mice) failed to reverse diabetes, whereas all PEC-DL (n = 22 mice) recipients maintained normoglycemia post transplant until the grafts were retrieved (arrow), at which point they reverted to their pretransplant hyperglycemic state. Shaded area represents a non-fasting physiological range (<11.1 mM). Dashed lines represent time frame in which recipients were implanted with insulin (Ins.) pellets. Data points represent blood glucose mean ± SEM.

(C, E, and G) Serum human C-peptide levels were collected 8, 12, and 20 weeks post transplant after an overnight fasting period and post-60 min intraperitoneal glucose tolerance test. All recipients demonstrated detectable C peptide; however, only recipients of PECs transplanted into DL site showed significant glucose-responsive C-peptide secretion (^∗∗p < 0.01, ^∗∗∗p < 0.001, paired two-tailed t test). Different letters represent significant difference between transplant groups through 8–20 weeks post transplant (a, p<0.05; b, p<0.01; c, p<0.001; one-way ANOVA with Tukey test for multiple comparisons). Data points represent C-peptide mean ± SEM (FP, n = 6 mice; SC, n = 5 mice; DL, n = 9 mice; each sample assayed in triplicate) and represented as box-and-whisker plots.